Yale ASH 2021 Highlights: Classical Hematology

Transcript

• 00:00Welcome to the Yale Ash 2021 highlights.
• 00:06My name is Bob Bone.
• 00:07I'm one of the hematologist at Yale,
• 00:09and I'm happy to facilitate
• 00:11this session today.
• 00:12As we are focusing on some of the important
• 00:16abstracts from the previous ash meeting
• 00:19relating relating to classical hematology.
• 00:21And today we have 3 presenters who will
• 00:24each present abstracts for about 15 minutes.
• 00:27We'll take questions at the end of the
• 00:29session and they should be entered
• 00:30into the chat room or to the Q&A.
• 00:32Before we start, let me take a
• 00:35moment to introduce our presenters.
• 00:38First Kelsey Martin,
• 00:39who is an assistant professor in clinical
• 00:42medicine at the Yale School of Medicine,
• 00:44and she practices hematology oncology
• 00:46at the Orange Care Center and has a
• 00:49special interest in classical hematology,
• 00:51and particularly the intersection
• 00:53of obstetrical care and hematology.
• 00:55Doctor Sudhanshu Mulay who is the
• 00:58medical director of the anticoagulation
• 01:00clinic at Saint Francis Hospital
• 01:03and Medical Center and he also has
• 01:06a strong interest in classical
• 01:07hematology and transfusion medicine.
• 01:09He's an assistant professor of medicine
• 01:11at the University of Connecticut.
• 01:13And then finally Doctor Alex Pine,
• 01:16who's assistant professor of medicine
• 01:18and hematology at the VA Medical Center.
• 01:22He and his colleagues have done
• 01:24significant work over the past few years,
• 01:26detailing the mechanisms of
• 01:30COVID Coagulopathy.
• 01:31So without further ado,
• 01:33I'll introduce Doctor Martin and
• 01:34let her begin the presentations.
• 01:40Great, thank you so much.
• 01:52Good afternoon everyone.
• 01:54Is my volume OK? Correct, alright,
• 01:57I'm going to be discussing A3 abstracts
• 02:00relating to bleeding disorders.
• 02:04First, abstract is titled efficacy and
• 02:07safety of the two Serin prophylaxis,
• 02:10a small molecule RNA interference
• 02:13therapeutic in a multicenter phase.
• 02:15Three study called Atlas I NH in people
• 02:19with hemophilia A or B with inhibitors.
• 02:22This was presented at the plenary
• 02:24scientific session by Doctor Gayoung
• 02:26from University of Southern California.
• 02:311st, I'll provide some background.
• 02:33Hemophilia A&B are rare bleeding
• 02:35disorders that are characterized
• 02:37by ineffective clot formation,
• 02:39largely due to impaired thrombin generation.
• 02:41As a result of severe
• 02:43deficiency of factor 8 and 9.
• 02:46Currently our standard of care largely
• 02:49relies on replacing the missing factor.
• 02:51There is a high rate of development
• 02:54of anti factor inhibitors which
• 02:55is up to about 30% in some of our
• 02:58patients with hemophilia A and about
• 03:005% of the patients with hemophilia B.
• 03:05Subcutaneous fat isran
• 03:06is a novel therapeutic.
• 03:08It's a small molecule RNA
• 03:11interference therapeutic that acts
• 03:13by binding and degrading at the M
• 03:15RNA which encodes for antithrombin,
• 03:17thereby partially silencing
• 03:19the expression of antithrombin.
• 03:22This rebalances hemostasis and
• 03:24restores thrombin generation in
• 03:26patients with hemophilia or A
• 03:29and has been demonstrated to be
• 03:31effective in patients with or
• 03:33without inhibitors as I'll discuss.
• 03:35This study demonstrated that
• 03:37prophylactic use of the two
• 03:39strands significantly reduced
• 03:41annualized bleeding rates,
• 03:43which is essentially bleeding
• 03:44events on an annual basis in
• 03:47patients with hemophilia A or
• 03:49hemophilia B that have inhibitors,
• 03:51and demonstrated both efficacy
• 03:54and safety data.
• 03:56In this study,
• 03:5757 patients were randomized,
• 03:582 to one in an open label phase.
• 04:00Three trial patients were
• 04:02males over the age of 12,
• 04:05again with either hemophilia A or B,
• 04:07with with inhibitors,
• 04:08and these were patients that
• 04:10had been receiving on demand
• 04:12treatment with bypassing agents
• 04:14for Blake breakthrough bleeding.
• 04:18There was 38 patients in the phase, two
• 04:20Syrian group and the dosing of this medic.
• 04:22This is a subcutaneous therapy that
• 04:24was given at 80 milligrams once a
• 04:27month versus 19 patients in the
• 04:30on demand bypassing Agent Group.
• 04:32They were followed.
• 04:33The primary endpoint was looking at annual
• 04:35bleeding rate in the efficacy period,
• 04:37which was nine months.
• 04:40Secondary endpoints looked at
• 04:42spontaneous bleeding rates,
• 04:44joints, bleeds,
• 04:45quality of life metrics,
• 04:47which by a validated quality of life
• 04:50tool and also frequency of the bleeding
• 04:53episodes that happened in the onset period,
• 04:55which was the first month of therapy as
• 04:57well as safety and tolerability data.
• 05:03And and this was demonstrated
• 05:05to be extremely effective
• 05:06in the future and patients.
• 05:08So you can see here on this first
• 05:10line the median annual annualized
• 05:12bleeding rate was actually 0.
• 05:17The estimated rate was 1.7 versus
• 05:21in the bypassing agent group.
• 05:23The median annualized bleeding rate was 16.8.
• 05:28And there was actually the median
• 05:31for spontaneous bleeds with zero
• 05:32in the future and category.
• 05:34There was also demonstration
• 05:36of significant quality of life
• 05:38improvements based on the validated
• 05:40quality of life screening tool.
• 05:44And it was effective in both
• 05:47patients with hemophilia A and
• 05:49in patients with hemophilia B.
• 05:51And we can see that 29 patients.
• 05:55And we received for two strand
• 05:57in the hemophilia A category
• 05:59and nine patients received it
• 06:01in the hemophilia B category.
• 06:02And again this is compared with
• 06:05the second second line here.
• 06:07But patient to receive that
• 06:09bypassing agent only with a
• 06:11very significant P value.
• 06:15Overall, the agent was well tolerated,
• 06:18although the main side effect of
• 06:21special interest was thrombotic events.
• 06:24Uhm? There was no deaths of any
• 06:29kind in either group of note.
• 06:32Of the patients that had thrombotic events,
• 06:34the authors reported that that
• 06:36occurred in some patients that
• 06:38seemed to have the antithrombin
• 06:39levels at the lower end of the range
• 06:41and seen some as low as 10 to 20%,
• 06:43and which is what they attributed to and
• 06:46only one patient who had a thrombotic
• 06:49event ended up coming off study,
• 06:50and this was a patient who had
• 06:53a thrombosis in a spinal vein.
• 06:56Other side effects were increases
• 06:59in transaminases,
• 07:00but the authors reported that this did not
• 07:02impact any of the treatment scheduling,
• 07:04and no patients had to come off trial for
• 07:06any changes in hepatic enzyme changes.
• 07:14So the conclusions were that the two
• 07:17Serin had significant improvements
• 07:19in the treatment arm compared with
• 07:21the on demand bypassing agents.
• 07:24And this is seen as somewhat of a
• 07:26game changer in the sense that it's
• 07:28given monthly and subcutaneous,
• 07:29which is a tremendous change in
• 07:31compared to the current standard
• 07:33of practice where patients are
• 07:35needing intravenous therapies and.
• 07:37In a much higher frequency.
• 07:40Nearly 2/3 of the patients treated with
• 07:42fattoush Rand had zero treated bleeds,
• 07:44and the mean median annualized
• 07:46bleeding rate was zero.
• 07:48And of note,
• 07:49this is also efficacious in both
• 07:51patients with hemophilia and hemophilia
• 07:53B and its patients with hemophilia
• 07:55B have really had not had similar
• 07:57prophylactic similar prophylactic
• 07:59options as our hemophilia A patients.
• 08:01So creating a new sort of treatment
• 08:05approach 7 patients in the treatment
• 08:07arm had at least one adverse event,
• 08:10including.
• 08:10The four thrombotic events and
• 08:11one of those patients did require
• 08:13withdrawal from this study.
• 08:18That concludes my discussion
• 08:19in the first abstract,
• 08:20and I'll move on to the second.
• 08:22The second abstract was titled
• 08:24rate of prolonged response after
• 08:26stopping THROMBOPOIETIN receptor
• 08:28agonist treatment in primary
• 08:30immune thrombocytopenia results
• 08:32from a nationwide prospective
• 08:34multicenter interventional study.
• 08:36And this was out of France.
• 08:43Some background information.
• 08:45There's been several retrospective
• 08:46studies and a recent prospective
• 08:48study that reported unexpected cases
• 08:51of durable remission after TPO
• 08:53receptor agonist were discontinued
• 08:54in adult patients with ITP.
• 08:56This has been seen in up to up
• 08:58to 30% of these patients.
• 09:00However, it felt that perhaps some of
• 09:03the newly diagnosed ITP cases in which
• 09:05such spontaneous remissions occurred,
• 09:07may may have been included
• 09:08in most of these studies.
• 09:12So the question this study has is what
• 09:15proportion of patients with either
• 09:17persistent or chronic phase ITP and no
• 09:20recent exposure to any potentially curative
• 09:23therapy such as splenectomy or rituximab,
• 09:25achieve a long term remission off
• 09:28treatment at 24 weeks and 52 weeks.
• 09:31After having on at least three months
• 09:33of their TPO receptor agonist exposure,
• 09:36who had a complete response
• 09:38and persistent phase,
• 09:39ITP is is defined as those with
• 09:42ITP between 3 and 12 months,
• 09:44whereas chronic phases lasting for beyond 12.
• 09:48Months, so the inclusion criteria.
• 09:51So again, this was a nationwide prospective
• 09:53multicenter interventional study.
• 09:55The inclusion criteria included
• 09:56patients over the age of 18 with either
• 09:59persistent or chronic primary ITP.
• 10:02They needed to have a stable
• 10:04complete response,
• 10:04which was defined as a platelet
• 10:06count of more than 100,000 for more
• 10:08than two months on their on their
• 10:11TPO RA therapy and they needed to
• 10:13have been on treatment with their
• 10:15TPO RA for at least three months.
• 10:17Exclusion criteria was patients
• 10:19who are on either anticoagulation
• 10:21or antiplatelet therapy.
• 10:23A patient who had previously failed the
• 10:25TPRA agent and the patient could not
• 10:28have been receiving any concomitant
• 10:30steroid or cortico steroid or IVIG,
• 10:33and they could not have had Rituxan mab,
• 10:35nor splenectomy within either the
• 10:36two months preceding or after
• 10:38initiation of their TPO or RA therapy.
• 10:43And the patients underwent a progressive
• 10:46dose reduction and they had to.
• 10:48There are TPO therapy or a therapy
• 10:50had to be stopped by 10 weeks and
• 10:53they proposed a method whether
• 10:54it was a Rama, Plasty, Morrell,
• 10:56Trumbo bag of of a protocol of how to how
• 11:00to taper off their doses accordingly.
• 11:02And if a patient relapsed during
• 11:04after this discontinuation,
• 11:05the decision to start a new therapy was
• 11:07left at every investigators discretion,
• 11:09and so the primary endpoint was
• 11:11what was the proportion of patients
• 11:13who achieved an overall response,
• 11:15which was defined as CR plus R
• 11:17at week 20 at week 24.
• 11:18So six months afterwards,
• 11:20and the secondary outcomes looked at those,
• 11:22the overall response rate after
• 11:24a year or 52 weeks, they look.
• 11:26I didn't looked at patients
• 11:27who had bleeding events,
• 11:28and they aimed to try to identify
• 11:30any predictive factors to see which
• 11:32patients might be those who achieve.
• 11:34Such an overall prolonged response.
• 11:39So 49 patients which included a 30
• 11:44females with either persistent.
• 11:45There was an end of two
• 11:47or chronic and a 47 ITP.
• 11:49The median age of 58.5 years were evaluated
• 11:53in this two year period over 22 centers.
• 11:5640 of the patients had received
• 11:59eltrombopag and nine around the plastic.
• 12:01And intention to treat analysis
• 12:0456.2% so 27 of the 48 patients
• 12:07achieving the primary endpoint
• 12:09achieved the primary endpoint and
• 12:12maintained an overall response at 24
• 12:14weeks after TPO RA discontinuation.
• 12:16And of those, half of those,
• 12:18essentially 55 percent, 15 of those,
• 12:2027 had a complete response,
• 12:23which again is defined as a
• 12:25platelet count over 100,000.
• 12:27Bleeding events did occur in 61.9% of
• 12:30the patients and 65.2% of the patients
• 12:33who did relapse at the 24 week and 50.
• 12:39Should be weeks or 52 weeks with the median
• 12:41platelet count of 31,000 at that time.
• 12:44No severe bleeding episodes occurred.
• 12:49And they could not identify any
• 12:52predictive factors. Neither age.
• 12:53Which agent the patient had,
• 12:55how long they'd had.
• 12:56ITP none of these things were
• 12:58able to predict which patients
• 12:59were those who were going to
• 13:01achieve such a sustained response.
• 13:03So the conclusions of this was
• 13:05that after 52 weeks and this is
• 13:07you can seen by the diagram on the
• 13:09right hand side after after TPR,
• 13:11a discontinuation overall response was
• 13:14seen in about half of these patients,
• 13:1752.1% for those who did relapse.
• 13:20The median time of relapsing after
• 13:22tapering was at about 8 weeks,
• 13:24but the majority of those actually
• 13:25happened within the first two weeks,
• 13:27and none of those patients who
• 13:29relapsed developed severe bleeding.
• 13:33In among 21 patients who did
• 13:36relapse before week 2413,
• 13:37of those were able to be re challenged
• 13:39with their TPO RA and they were still
• 13:42able to achieve a complete response
• 13:44with a medium time of two weeks.
• 13:48So the conclusion is that there was a
• 13:50high rate of sustained off treatment
• 13:52remission after TPO RA discontinuation
• 13:54in patients with chronic ITP who had
• 13:57initially achieved at stable CR.
• 13:58They were unable to die and identify a
• 14:01predictive factor of which patients were
• 14:03would achieve such a lasting remission.
• 14:06But this study strongly supports use
• 14:08of a progressive tapering off of the
• 14:10dose of TPRS and patients who do
• 14:11achieve a stable CR on treatment.
• 14:13And there may be opportunity for us
• 14:15to be able to discontinue therapy
• 14:16in such patients.
• 14:21The last abstract I'll discuss
• 14:23was called obstetric obstetrical
• 14:24and perioperative management of
• 14:26patients with factor 11 deficiency.
• 14:28A retrospective observational study.
• 14:33In the background information
• 14:35data regarding obstetrical and
• 14:37perioperative management of
• 14:38factor 11 deficiency is scarce.
• 14:42And the question at hand is,
• 14:43can we create a database of such patients
• 14:46and identify factors associated with
• 14:47increased increased bleeding risk in
• 14:50patients with factor 11 deficiency
• 14:52during childbirth or surgery?
• 14:53And this was presented by Doctor
• 14:55Hanna from the Icahn School
• 14:56of Medicine at Mount Sinai.
• 15:01So they did a retrospective chart
• 15:02review of patients with factor 11
• 15:04deficiency who underwent either
• 15:06childbirth or surgical procedures over
• 15:08a 10 year period within the Mount Sinai
• 15:10health care system in New York City,
• 15:12and they collected data on age, sex,
• 15:15ethnicity, genotype, family history,
• 15:17personal history of bleeding.
• 15:19The type of anesthesia used the
• 15:21estimated blood loss and any evidence
• 15:23of of periprocedural bleeding
• 15:25which patients needed blood product
• 15:27administration and which product
• 15:29which patients needed hemostatic
• 15:31agents in the perioperative period,
• 15:34they defined a bleeding endpoint as acute
• 15:37postpartum or post operative hemorrhage,
• 15:39or any bleeding that warranted
• 15:41non prophylactic administration
• 15:43of pack red blood cells.
• 15:45FFP or tranexamic acid.
• 15:48They performed a logistic regression
• 15:49to test for the association
• 15:51between either historical,
• 15:52laboratory and procedural variables
• 15:54with the bleeding endpoint.
• 15:58So overall, 198 patients were evaluated
• 16:01who had undergone 252 procedures in total.
• 16:05This included 143 vaginal
• 16:07deliveries in 64 city sections
• 16:09and 45 other surgical procedures.
• 16:1238 of the 252 procedures did
• 16:15result in bleeding complications,
• 16:17and they found that both a prior
• 16:19history of bleeding and a lower
• 16:21factor 11 levels were independently
• 16:23associated with the bleeding endpoint.
• 16:28Interestingly, 8 out of 21 patients,
• 16:3138% who suffered a bleeding complication.
• 16:34This happened despite prophylactic FFP.
• 16:38The mean factor level level for
• 16:40with patients who receive neuraxial
• 16:42anesthesia was 50 units per deciliter.
• 16:45In five patients with a
• 16:47negative bleeding history,
• 16:48despite surgical challenges,
• 16:49we're actually able to receive
• 16:52neuraxial anesthesia effector
• 16:53level levels less than 10 and
• 16:55without any bleeding complications,
• 16:57and only one of these had
• 16:59received prophylactic FFP.
• 17:05So their conclusions were that a personal
• 17:07history of bleeding was the strongest
• 17:10predictor of perioperative or obstetrical
• 17:11bleeding and and that personal history of
• 17:14bleeding was was actually defined as just
• 17:16one one report of heavy menstrual period
• 17:18or bleeding in the operative period.
• 17:20It just took sort of one one event in time to
• 17:23define a personal history of bleeding factor.
• 17:2611 levels were found to correlate with a
• 17:28slightly slightly lower but statistically
• 17:30significant odds of surgical bleeding,
• 17:32and they found that a factor
• 17:3411 level cutoff of 40 units per
• 17:36deciliter may predict bleeding risk.
• 17:37With reasonable specificity at
• 17:4083% but lacked sensitivity,
• 17:41they also found that factor 11
• 17:44levels are stable during pregnancy,
• 17:46as demonstrated by the diagram
• 17:48on the bottom right,
• 17:50showing that repeat measurements
• 17:51may not be necessary,
• 17:52which is something commonly done in practice,
• 17:56and they also found that neuraxial anesthesia
• 17:58appeared to be safe to use in this cohort,
• 18:01which clinically is a question
• 18:03that comes up frequently.
• 18:04Hey, thank you for your time.
• 18:07Forward to hearing from our next speaker,
• 18:09Doctor Malik.
• 18:13Thanks, Kelsey.
• 18:26Right, thank you for the
• 18:29opportunity to talk today.
• 18:31I'm going to focus on thrombosis,
• 18:34so I'm hoping to present three
• 18:36studies that I found of interest.
• 18:40Have one focus study and then as
• 18:42time permits and go through the
• 18:45other two studies with quickly.
• 18:47The focus state I would I would
• 18:49like to present is 1 listed here
• 18:52by Murs ET al from the Brigham
• 18:55and Women's Hospital in Boston who
• 18:58looked at anticoagulation use and
• 19:00outcomes among patients with atrial
• 19:03fibrillation and vanilla brand disease.
• 19:07Oral presentation.
• 19:09The background is that estimated
• 19:12prevalence of symptomatic 1 willibrand
• 19:15disease is about one in 1000.
• 19:18It is estimated that.
• 19:21Patients with one milligram
• 19:23disease have similar prevalence
• 19:25of atrial fibrillation as general
• 19:27population is about .84%.
• 19:30The American College of Cardiology
• 19:32recommends using anticoagulation for those
• 19:34with atrial fibrillation who have chads,
• 19:37vascor of two or greater in men
• 19:39or three or greater in women.
• 19:41The recent ash ISTHNHF&W SH guidelines
• 19:48recommend using anticoagulation or
• 19:51antiplatelet therapy as clinically indicated.
• 19:54It was a suggestion with low certainty
• 19:57of evidence and importantly when
• 19:59I looked into the the actual.
• 20:04Basis of this recommendation,
• 20:06it was based on a case series of about
• 20:0960 patients or really low quality data.
• 20:14So this the study that was
• 20:16presented was a retrospective study
• 20:18in which data was obtained from
• 20:21the Electronic medical records.
• 20:23Patient was selected if they had
• 20:25a diagnosis of 1 lip and disease
• 20:27noticed or seeking cofactor activity
• 20:29or any abnormal one will event factor
• 20:32measurements and also selected for those
• 20:35who had diagnosis of atrial fibrillation.
• 20:38The primary endpoint was rate of major
• 20:40bleeding as defined by the IST criteria,
• 20:43which is fatal.
• 20:44Bleeding, bleeding in critical
• 20:46organs or bleeding causing more
• 20:48than two grams of two grams per DL,
• 20:51drop in hemoglobin or more than two
• 20:54units of red blood cell transfusion.
• 20:55Sorry with the typo.
• 20:58The results were that patients in
• 21:02tribulation patients were between
• 21:05diagnosed between 1980 and 2020.
• 21:09For 340,
• 21:10patients were screened and
• 21:1189 patients were selected.
• 21:13For the final analysis.
• 21:15Out of those 64 patients were female,
• 21:1828% patients were deceased at
• 21:20the time of the data pool.
• 21:22Medium Chance Best Score was three and 89,
• 21:26so close to 90% had a score of two or higher.
• 21:30A third of the patients also had
• 21:32a quote acute coronary syndrome,
• 21:34which the authors lumped together
• 21:36STEMI non STEMI and Angela.
• 21:41In the in the figure over here as we can see,
• 21:4542.7% of the patients in the
• 21:48study were on aspirin or they
• 21:50were ever prescribed aspirin.
• 21:52About 13.4% of the patients were ever
• 21:57prescribed P2Y2 inhibitors and 56.2%
• 22:01were ever prescribed an anticoagulant.
• 22:05The green color represents people
• 22:08with antiplatelet agents who also had
• 22:12diagnosis of acute coronary syndrome.
• 22:14About 1/4 of the patients were
• 22:17never prescribed any anticoagulant
• 22:19or antiplatelet agent.
• 22:23In these two graphs we can see the
• 22:26median time to 1st bleeding event
• 22:28on the left we have antiplatelet
• 22:31agents and on the right it's
• 22:33anticoagulants as we can see in both.
• 22:36It looked like the the median or
• 22:40the time taken for median first
• 22:42meeting was greater than 15 years.
• 22:44For both of these study groups.
• 22:49Just going into the raw numbers,
• 22:5310.2 events per hundred patient years.
• 22:56So the rate of major bleeding was
• 22:5810.2 events per hundred patient years.
• 22:59For those on platelet agents,
• 23:028.9 events per hundred person years.
• 23:05For those on anticoagulants
• 23:07without any statistical
• 23:08difference between the two groups.
• 23:10Baseline risk of bleeding was one
• 23:12event per hundred patient years,
• 23:15so these were the patients who
• 23:17never got antiplatelet therapy
• 23:19or anticoagulant therapy.
• 23:21Concomitant anticoagulant and
• 23:22antiplatelet agents resulted in
• 23:24much higher risk of bleeding,
• 23:26which was about 28 events
• 23:28per hundred patient years.
• 23:30The lifetime risk of major beating was
• 23:33also calculated by the investigators,
• 23:35which was 32% in those who were
• 23:39ever prescribed anticoagulants,
• 23:41and 25.6% who were never
• 23:44prescribed anticoagulants,
• 23:45and there was no statistical
• 23:47difference between the two groups.
• 23:51Looking at the stroke risk,
• 23:52the incidence of stroke was
• 23:55about 15 point 7%. And notably,
• 23:5811 out of the 14 patients had
• 24:00never used and equivalent for more
• 24:02than sorry had not been prescribed
• 24:05anticoagulant for 90 days or more.
• 24:08The median chance best score was
• 24:09three in those who had stroke.
• 24:14And and also those who are
• 24:17not anti quietly therapy.
• 24:19One of those patients who had
• 24:21a stroke had a fatal stroke.
• 24:26So the authors concluded that 50% of
• 24:28the patients in their study group
• 24:31were ever prescribed anticoagulant.
• 24:34There was no benefit in choosing anti
• 24:37platelet therapy or anticoagulant therapy
• 24:39if bleeding rate is taken into account.
• 24:43There was no difference in lifetime
• 24:44risk of bleeding in those who were
• 24:47prescribed anticoagulants versus those
• 24:48who were not prescribed anticoagulants.
• 24:51Limited use of anticoagulant and antiplatelet
• 24:54therapy has much higher risk of bleeding,
• 24:57which is not surprising and 57% of
• 25:01patients had thromboembolic strokes.
• 25:03Most of those who were not therapy.
• 25:07So my take away from this study
• 25:08was that it was one of the largest
• 25:11studies looking specifically at this
• 25:13population of one will appendices.
• 25:15Individuals who also have April fibrillation.
• 25:18It was a retrospective study,
• 25:19so has its own limitations,
• 25:21but it still provides one of the
• 25:24largest studies or largest evidence,
• 25:27which makes us probably feel a little
• 25:29bit more comfortable using anticoagulant
• 25:31in these patients with appropriate risk.
• 25:34Assessment of bleeding.
• 25:37Oftentimes antiplatelet agents are
• 25:40prescribed over antique violence as
• 25:42a way to reduce the risk of bleeding,
• 25:44but this study sort of makes
• 25:47us doubt that assumption.
• 25:48Details of 1 milligram disease
• 25:51subtypes were missing,
• 25:52and as we know,
• 25:54the severity of lung disease or
• 25:56the type of 1 disease could make a
• 25:58difference to the bleeding risk.
• 26:00We also have noted recently that
• 26:03ristocetin cofactor activity may not
• 26:05be appropriate to diagnose patients
• 26:07with type 21 blip and disease,
• 26:09so some of those individuals were
• 26:11typed as one group and disease back
• 26:13in the previous years may actually
• 26:15not have one web and disease.
• 26:18Similarly,
• 26:18practice patterns for A-fib management
• 26:20as well as the choice of anticoagulation
• 26:23has changed quite a bit since 1980s,
• 26:26so that would certainly people founder.
• 26:31We're gonna move on to the next.
• 26:34So this was a man and also an
• 26:38oral presentation.
• 26:39Presented on behalf of Doctor Connors.
• 26:44It was it was a meta analysis of
• 26:47direct oral anticoagulants versus low
• 26:49molecular weight heparin for treatment
• 26:52of cancer associated thrombus.
• 26:57In the in this study, the authors
• 27:00looked at 6 randomized control trials.
• 27:04The. This was an update to
• 27:07the previous meta analysis,
• 27:08which had four of these trials
• 27:10mentioned over here. The top four.
• 27:12So the two bottom ones were
• 27:14included in this meta analysis,
• 27:16so there were a total of 3690 patients
• 27:20out of which 1850 got direct oral
• 27:23anticoagulants and 1840 got local.
• 27:28The authors looked at the risk of
• 27:31recurrent venous from embolism,
• 27:32and it favored use of
• 27:35direct oral anticoagulants.
• 27:37Incidence rate of recurrent VTE was 5.5%.
• 27:43In the electrolytic group
• 27:44and eight point 3% in the low
• 27:47molecular Weight Heparin group.
• 27:50With the risk ratio of .67 favoring director.
• 27:57Risk of major bleeding was about
• 27:59the same in the two groups,
• 28:02so the incidence was four point 3%
• 28:05in the direct oral anticoagulants
• 28:06group and three point 7% in the low
• 28:09molecular Weight Heparin group.
• 28:11And statistically, there was no
• 28:13difference between the two groups.
• 28:14The clinically non the clinically
• 28:18relevant non major bleeding.
• 28:20Favored use of heparin,
• 28:22so it was the incidence was 9.5%
• 28:28of this bleeding in the direct or
• 28:31anticoagulant group and five point 7% in
• 28:33the low molecular weight heparin group.
• 28:35The risk was 1.6 and statistically favoring
• 28:38low molecular weight heparin group.
• 28:43All 'cause mortality was
• 28:44similar in the two groups.
• 28:47The conclusions drawn from this study
• 28:50of from this paralysis for that to
• 28:53act significantly reduce the risk of
• 28:55recurrent VTE compared with heparin,
• 28:57without increasing the
• 28:59risk of major bleeding.
• 29:01However, use of direct oral
• 29:03anticoagulants was associated
• 29:04with increased risk of clinically
• 29:06relevant non major bleeding.
• 29:10Finally, the last oral study that I
• 29:14would like to present was about impact
• 29:18of race and ethnicity on cancer,
• 29:20associated thrombosis among
• 29:22underserved patients with cancer.
• 29:24This was an oral presentation
• 29:26presented by Doctor Decosta.
• 29:30In this study, a retrospective
• 29:33analysis was done and the investigators
• 29:38identified 9353 patients.
• 29:41After those, 49.3% were Hispanics,
• 29:4527.6% were non Hispanic blacks,
• 29:4850.5% were non Hispanic
• 29:50whites and 7.6% were passed.
• 29:53Islanders interestingly,
• 29:5774.7% were uninsured, and.
• 30:01The reason for this was the
• 30:03study was primarily focused on a
• 30:05safety net hospital in Houston,
• 30:07which has this demographic of population.
• 30:11The incidence of cancer associated
• 30:13thrombosis was seven point,
• 30:153% at six months and 9.6% at 12 months.
• 30:19Of previous studies which
• 30:21have looked at this,
• 30:22which were primarily focused
• 30:25on Caucasian population,
• 30:26the risk at 12 months is much lower,
• 30:30about 2.3%.
• 30:30So something to keep in mind.
• 30:35On the graph on the left,
• 30:37we can see, as expected,
• 30:39pancreatic upper GI where the OR
• 30:42patients with pancreatic or upper GI
• 30:44cancers were the ones with highest
• 30:47risk of cancer associated thrombosis.
• 30:49The interesting part was the top.
• 30:51Sorry, the bottom right figure where
• 30:54we can see that non Hispanic black
• 30:57population and non Hispanic white
• 31:00population seem to have similar
• 31:02cumulative incidence of cancer
• 31:04associated thrombosis at 12 months.
• 31:06While Hispanic population and Asian
• 31:10population seem to have a lower risk,
• 31:13so this contradicts what we have
• 31:16traditionally known about thrombosis,
• 31:18which is reported to be higher in
• 31:23individuals with black ancestry.
• 31:25And Hispanic population have
• 31:27been traditionally known to have
• 31:28a lower risk of thrombosis,
• 31:30so that is congruent with that knowledge.
• 31:36When the authors did the
• 31:38multivariable analysis,
• 31:39they again found Hispanic race
• 31:42and Asian race were to have an
• 31:46impact on the risk of getting
• 31:48cancer associated thrombosis.
• 31:52The conclusions drawn were
• 31:54higher incidence of cancer.
• 31:55Associated thrombosis was noted
• 31:57compared to the European registries.
• 32:00Non Hispanic blacks had similar
• 32:03incidence of cancer associated
• 32:05thrombosis to non Hispanic whites.
• 32:08Hispanic and Asian Pacific Islanders
• 32:09had a lower risk of cancer associated
• 32:12thrombosis compared to non Hispanic
• 32:14whites and non Hispanic black population.
• 32:17And treatment with chemotherapy
• 32:19or immunotherapy associated.
• 32:21It would help you or immunotherapy was
• 32:24associated with increased risk of thrombosis.
• 32:27That concludes my talk.
• 32:33You said that she.
• 32:48I'm just gonna start my groups.
• 32:53The right one.
• 33:02Hopefully this is the right one.
• 33:05Alright, I'm so let me just start moving.
• 33:10OK so hello buddy and Alex Pine and I
• 33:15wanted to briefly briefly everybody
• 33:18on 3 potentially 4 abstracts.
• 33:21If we have time and.
• 33:25The first three are sort of have
• 33:28this ITP flavor and a couple
• 33:30of them has kovid color,
• 33:32so the first one is actually the
• 33:36first two kind of have the same motif,
• 33:39and they both studies actually looked into.
• 33:45What happens to patients with
• 33:47persisting thermoset opinion
• 33:49when they receive COVID that
• 33:52vaccines and so the first study?
• 33:56Which was out of Cornell.
• 33:59Essentially they were operating
• 34:01on the premise that play,
• 34:04let's play play quite a bit of
• 34:07a role in immune immune system.
• 34:11And also in their cohort,
• 34:15different cohort but in their center
• 34:17thrust opinion happened in 27% of
• 34:21patients with just COVID-19, so they.
• 34:24Actually postulated,
• 34:25or at least developed the concept further.
• 34:30That in COVID-19,
• 34:32especially severe COVID-19, there's a a.
• 34:35This is normal glycosylation of the
• 34:37spike protein antibodies is is a
• 34:40prothrombotic signal for platelets,
• 34:41especially through.
• 34:46Direct receptor these complexes of
• 34:49IgG and virus operate through the
• 34:53Cy come receptor and So what they?
• 34:59They also. There was also a
• 35:02clinical sort of observation.
• 35:04Then there were some reports of ITP in post
• 35:07vaccine settings in a single institution.
• 35:10I believe I'm GH.
• 35:11There was a 52 patients and there
• 35:13were 12% of ITP dissertations.
• 35:16So they asked the question.
• 35:19Several questions is in fact what is the
• 35:21effect of vaccines on platelet count,
• 35:23risk of bleeding events?
• 35:26What kind of what kind of effect
• 35:30is in repeat dosing of vaccines?
• 35:31You know the second vaccine
• 35:33booster and so on,
• 35:34and what the risks of
• 35:36the actual exacerbation.
• 35:37What sort of plays a role in
• 35:39exacerbating so their cohort was
• 35:44retrospective from patients 10
• 35:46university affiliated patients
• 35:48that we actually also participated.
• 35:50So it's 117 patients.
• 35:54With a pretty long history of ITP 12 years.
• 35:57And of course they were.
• 36:00You know at the time where the
• 36:01study was sort of conducted,
• 36:03yeah,
• 36:04the patients were getting vaccinated
• 36:07were older patients.
• 36:09So breakdown of what therapies
• 36:13were administered,
• 36:14either on therapy or off therapy
• 36:17or prior prior therapy.
• 36:18So
• 36:21TPO, RA's and we talk smack word
• 36:25bulk of the of the treatments,
• 36:27and colectomy was also in 21% of
• 36:29patients and at the time of the study 40
• 36:32patients were off treatment and 16 of
• 36:35those were with normal platelet count.
• 36:37This is a breakdown of.
• 36:39See the exchange that we received.
• 36:43Simon, of course majority and
• 36:45then definitions how they sort
• 36:47of were assessing the response.
• 36:49So stable platelet count was plus
• 36:51minus 20% of the pre vaccine level,
• 36:53and ITP exasperation was defined as either.
• 37:01Much higher than 50% reduction of
• 37:04platelet count or 20% reduction if you.
• 37:08If the if the native platelets
• 37:10below 30,000 or the use of rescue
• 37:13treatment and So what?
• 37:16They found that there's a
• 37:18three groups of patients.
• 37:20So in about.
• 37:23I would say third or close to third
• 37:27quarter places actually increased
• 37:29platelet count increased in.
• 37:31Happened in middle part like a 40%.
• 37:34Nothing happened and in
• 37:36about third so to speak,
• 37:39it's actually decreased and this is
• 37:41the first Test of the second dose.
• 37:43Sort of similar and they pointed out
• 37:46that it may not be the same patience.
• 37:49So they broke it down into
• 37:53into into several groups.
• 37:56Specifically,
• 37:56so they assessed all patients in
• 38:00terms of incidence of post vaccine
• 38:02ITP reservation splenectomy patients,
• 38:04patients with me in patients with very
• 38:06heavily pretreated with five more than five,
• 38:08five, and more prior therapies,
• 38:11and so,
• 38:12interestingly enough,
• 38:12if you look at this point to me,
• 38:15it's they they saw a significant
• 38:19significantly higher incidence of.
• 38:25I've played loads of ITP reservations
• 38:29as well as patients with who are
• 38:31very, very heavily pretreated.
• 38:36Now when the when the post vaccine
• 38:38rescue therapy was administered,
• 38:39it was it was effective was administered
• 38:41about 30% of patients and they they
• 38:45reported no serious bleeding events.
• 38:47From a patient with.
• 38:52Patients with stable or
• 38:54increased platelet count after.
• 38:57The first vaccine,
• 38:58so that was those 43 patients,
• 39:01and after those number 26 patients have
• 39:05platelet count, decreased below 30.
• 39:09So factors that are found not
• 39:11predictive of estimation were age,
• 39:13gender, vaccine type and
• 39:15presence of autoimmune disease.
• 39:18They actually had access to two
• 39:21surveys and they sort of tried.
• 39:23They tried to validate their findings
• 39:26and they they looked into these surveys.
• 39:31These are two surveys.
• 39:32One is from a base in the United States,
• 39:35one is from UK especially.
• 39:36They track the track.
• 39:40Similar data. And so they found
• 39:44that in indeed in patients who
• 39:47had platelet count decreased.
• 39:50There were a lot more
• 39:52people with splenectomy.
• 39:54And then when they looked
• 39:57into your CTP cohort.
• 40:00Also survey based they found
• 40:03sort of breakdown of similar.
• 40:06Similar breakdown of decreased
• 40:07platelets about the third of patients
• 40:10indeed had ITP assassinations,
• 40:11and they also in the same
• 40:13survey found this book to me.
• 40:15Was the shade with a 2 fold
• 40:17increase of risk of decreasing
• 40:19in platelets by more than 50%.
• 40:21So they acknowledged the speed
• 40:23limitaciones that there's no lack of.
• 40:26There's there's no unvaccinated
• 40:29control group 2.
• 40:31To compare,
• 40:31there was a possible selection
• 40:33bias because they were following
• 40:35a lot closer to the people who
• 40:36are had refractory GP already.
• 40:40They were they didn't account
• 40:42for titration for concurrent sort
• 40:43of interventions in terms of how
• 40:45they affect the platelet count,
• 40:46including the titrations of the of
• 40:48the medications of the treatment
• 40:50that the patients were already on,
• 40:52and the technology that the possible
• 40:54overlap between cohort might effect
• 40:56might affect the platelet count,
• 40:58but overall they felt that the
• 41:00major point was that there was
• 41:03no bleeding in refractory TCP
• 41:05in refractory thrombocytopenia.
• 41:07Following vaccination and the major.
• 41:12.0 there was like if it's
• 41:14if it's a splenectomy.
• 41:15Patients follow closer.
• 41:16If it's a patient,
• 41:17were the difficult control
• 41:19ITP or heavily pretreated.
• 41:20Follow them closer.
• 41:23And so that was main main idea and then
• 41:28in a sort of in the in the in the post
• 41:31in a additional question sort of session
• 41:34following the abstract presentation.
• 41:35Somebody was asking, how would you counsel
• 41:38consultations and who actually did not,
• 41:40perhaps did not who I had
• 41:43from Selena after the first.
• 41:44Actually would you, you know,
• 41:45give the second vaccine, and so the
• 41:48presenter actually said that she usually.
• 41:52She would actually recommend
• 41:54but with close observation.
• 41:56Alright, so moving on to the second
• 41:58one so the second study was similar.
• 42:01In fact, they just followed one another.
• 42:03This one is from.
• 42:05Dutch study the benefit of this
• 42:07study was a prospective cohort,
• 42:09but the question was fairly similar
• 42:11to what happens in patients with
• 42:14ITP with pre-existing ITP when
• 42:16they receive COVID-19 vaccine.
• 42:18This study had a control arm.
• 42:21It had about a similar twice
• 42:24as much patients,
• 42:26218 in about the same number of 200.
• 42:29Healthy controls.
• 42:30Breakdown of vaccine was a little different,
• 42:33most of them received Moderna that was.
• 42:36Holland come in.
• 42:37All healthy controls received.
• 42:40Moderna 15 patients required
• 42:42rescue treatment.
• 42:44Now this is a breakdown of the treatment
• 42:48that patients were received or were on.
• 42:53So quite a number were on steroids
• 42:55in at a time and then also
• 42:59about 10% were Hispanic to me,
• 43:02definition of ITP dissertation
• 43:04was fairly the same.
• 43:07In fact, exactly the same.
• 43:09And sorry and So what they?
• 43:12What they found here on the
• 43:15graph below is that the.
• 43:19Both pleasant count in both
• 43:22normal controls and in.
• 43:27Patient stated patients actually
• 43:28decreased and they I believe
• 43:31they said it's decreased by 6.3%
• 43:33in both in both in both groups,
• 43:36so they didn't really feel there
• 43:37was a difference in reduction,
• 43:39but they both platelets
• 43:41in both groups went down.
• 43:46In fact, this is the better image of that.
• 43:54And so they further look
• 43:55into risk factors as well.
• 43:57And here they found interesting piece
• 44:00which is a contradicts the previous study.
• 44:03They found that split me actually was
• 44:05associated with increase of platelets,
• 44:07quite substantial cruise of platelets.
• 44:10And a current treatment was associated
• 44:15with a decrease of platelets and.
• 44:18Age was associated with small decrease
• 44:21in platelets following vaccinations.
• 44:25So this is again sort of a tally that
• 44:283030 patients developing masturbations
• 44:3115 required rescue treatment.
• 44:34The bleeding they did report bleeding,
• 44:36and interestingly enough and and in
• 44:40a post in a in a in a in a question
• 44:43period they were asked about this,
• 44:46so all the five bleeding episodes
• 44:48happened in patients with platelet
• 44:50count of higher than 100,000.
• 44:52And in fact one patient who had a
• 44:56fatal fatal gastrointestinal bleeding
• 44:58also had platelet count of 100.
• 45:00So their answer was that it's.
• 45:05It was not related to vaccination at all,
• 45:06it was comorbidities,
• 45:07and in fact in the patients who
• 45:09had a GI bleed fatal jab bleed,
• 45:10it was a severe liver disease.
• 45:15Few patients require transfusions
• 45:17over plated or.
• 45:19It helps so the conclusions here is,
• 45:22it's actually kind of similar.
• 45:23The effect of code in vaccination
• 45:26is similar in health in healthy
• 45:28controls and ITP patients.
• 45:30Dissertations were only a
• 45:32few very few ITP patients.
• 45:34There was a good response
• 45:36to rescue treatment.
• 45:38And essentially vaccination is safe and
• 45:40monitoring is advised and is actually
• 45:43was recommended by ASH guidelines.
• 45:47Come and this is sort of the additional
• 45:49questions that they were asked.
• 45:51Somebody asked whether they check
• 45:52for platelet antibodies and they
• 45:54said they did not evaluate for
• 45:56platelet antibodies directly,
• 45:57but but there's no association with
• 46:01high levels in health healthy controls.
• 46:06So,
• 46:06so I want to just finish up with this
• 46:09third study, which is which is also.
• 46:14ITP related studying.
• 46:15In fact,
• 46:16this is an interesting trial about use
• 46:20of BTK inhibitor will support NIP in.
• 46:25A refractory relapsed ITP's.
• 46:27The premise of the of the of the trial
• 46:31was was I think it was five for face,
• 46:33face,
• 46:33one face,
• 46:34two sort of update on on on the
• 46:37phase one phase two trial.
• 46:38The the premise was that pertain
• 46:41inhibitors modulate quite a bit of a quite
• 46:44a number of different effector cells.
• 46:46B cells and macrophages.
• 46:49Then also signaling signaling of the
• 46:52basilar receptor and inhibitors decrease
• 46:55our reactive antibodies in so there's a.
• 46:59There's an interest in evaluating
• 47:01this group of class of medications.
• 47:04Class of drugs in it P.
• 47:06And specifically.
• 47:07While I'm really Brittany was chosen because.
• 47:12Is believed to be very selective,
• 47:13so out of different kinases
• 47:16it's it's pretty selective.
• 47:18It inhibits quite quite nicely, but.
• 47:23But not others, rather occupy.
• 47:27Target potentially, but not others.
• 47:29It's quite reversible.
• 47:32And why not in Britain for instance?
• 47:35Well,
• 47:35so there's association of
• 47:37play legation with liberty,
• 47:39but not as shown here when.
• 47:45Was tested against collagen
• 47:48so much much. He come.
• 47:54Specially associated with
• 47:56aggregation more than rules.
• 47:58So the trial instant criteria was
• 48:01fairly straightforward, its response.
• 48:03It's essentially adults response.
• 48:06They have to have at least had to have
• 48:09at least response to one prior treatment,
• 48:12and there's no other available
• 48:14to them or not approved.
• 48:16And there should be at least two platelet
• 48:19count less than 30 thirty thousand
• 48:22brother on 2 occasions and concurrent
• 48:26therapists were allowed, including.
• 48:28Storage entity arrays.
• 48:30There was a dose escalation as a phase one,
• 48:34but in kind of a phase two
• 48:36phase of it part of it they use
• 48:38actually 400 milligrams VID,
• 48:40which I'll show soon.
• 48:42Primary in point was essentially.
• 48:45Account of greater than 50,000
• 48:47on two occasion at least,
• 48:50and an increase of 2020 thousand of the
• 48:54baseline without use of rescue medication.
• 48:57And they actually had a long term
• 49:00extension also for 400 milligrams PID.
• 49:02And so here's what happened.
• 49:04So this is kind of a overall study diagram,
• 49:07so this is the 400 the ID group.
• 49:11So this is 45 patients.
• 49:13And so here's the results.
• 49:17So out of this 4518 that is 40% reached
• 49:21the primary endpoint so greater
• 49:23than 50 in with 20 greater than.
• 49:2850% fifty thousand increase.
• 49:31Sorry, greater than 50,000 platelet count
• 49:35increased 20,000 from the baseline,
• 49:37so that's 18 patients reached that end
• 49:39point and it was very rapid improvement,
• 49:42so this is it's probably hard to see.
• 49:45But this is days and so within,
• 49:48you know this is actually 20.
• 49:49I think it's 25 or 29 days,
• 49:52so it's a really rapid improvement
• 49:54and it's actually sustained.
• 49:55And of course these are not responders and
• 49:58you can see here that this is sort of a.
• 50:01Better.
• 50:03Way to assess sort of duration of response.
• 50:05So this is greater than 30 number
• 50:08of number of weeks achieved
• 50:10in 20 and then 15 and 14.
• 50:15So then, whoops.
• 50:21And so they made a point
• 50:23that it's indeed very rapid,
• 50:25very rapid increase in fact,
• 50:28median time to greater than 30,000
• 50:31level was achieved in 8.5 days
• 50:35greater than 30,000 + 20,000 above
• 50:37the baseline in basically 12
• 50:39days in greater than 50,000 play
• 50:41account in just about the same
• 50:4412.5 days and median time for the
• 50:46primary response was about a month,
• 50:48so it's very very rapid.
• 50:51And then they also showed the.
• 50:54What happened in this long long extension?
• 50:58Arms, so to speak,
• 50:59and they said that it's basically
• 51:02it was quite robust.
• 51:08Especially it's a.
• 51:10It's a maintain the maintained the
• 51:13response alright and then adverse effects.
• 51:17Basically it's all grade one grade,
• 51:19one grade, two diarrhea and nausea,
• 51:22fatigue. And again this is all
• 51:25about 400 milligrams twice a day,
• 51:27so conclusions. Mr.
• 51:31Bracnet provides.
• 51:34Inhibition of phagocytosis.
• 51:39And 40% of patients on 400
• 51:42milligram VID achieved endpoint
• 51:44primary endpoint at 18 patients.
• 51:46Response was rapid and was well
• 51:50tolerated and response was maintained.
• 51:53So there's open going
• 51:55face the Luna three trial,
• 51:56which further will address this.
• 52:01This this modality in additional questions.
• 52:06I think there was nothing really
• 52:08particularly interesting,
• 52:09but they said there's no,
• 52:10nobody, nobody was on any.
• 52:14Antibiotic prophylaxis and
• 52:16there was no infections.
• 52:18So I think in interest of time I finish,
• 52:20I stop here.
• 52:23If we have some questions, well,
• 52:25thank you all very much for those very
• 52:27informative and very clear presentations.
• 52:32If people do have questions,
• 52:33if they could put them in the chat
• 52:35that there are a couple there.
• 52:37Maybe we can start with those.
• 52:39So I'm Kelsey.
• 52:41You mentioned in your abstract with
• 52:43factor 11 deficiency that some patients
• 52:46bled despite getting fresh frozen plasma.
• 52:50What what might be some alternatives
• 52:52to treat those individuals?
• 52:53Or do you have any any thoughts about
• 52:55why those people still had bleeding?
• 52:58Yeah, it's interesting.
• 52:59I mean the half life of factor 11 is long.
• 53:03I think about two days or so,
• 53:04and so it's it's.
• 53:06It's intriguing, but I think something
• 53:07we've all experienced in practice.
• 53:09I think that may happen,
• 53:10perhaps just the quantity effect
• 53:12or Lebanon is not concentrated.
• 53:15You know, you never maybe know
• 53:17exactly what you're getting in the FP,
• 53:18and maybe one element.
• 53:20And I, you know there are
• 53:22cases reported of inhibitors,
• 53:23so perhaps some of those
• 53:24patients that didn't respond,
• 53:25maybe inhibitors.
• 53:28I think that I think Novoseven could be used,
• 53:33but I think with caution and maybe
• 53:34at a lower dose or maybe particularly
• 53:36in someone who had an inhibitor.
• 53:38I think there would be a role there,
• 53:39and then maybe sort of leaning more
• 53:42heavily on anti fibrinolytics might
• 53:44be useful, but I mean I think it's.
• 53:48A challenge we've all seen and experienced
• 53:50that sometimes is hard to pinpoint.
• 53:53It's a great question,
• 53:54great, thank you.
• 53:55Thank you and and Sudan shoe. You.
• 53:57You mentioned that there was an
• 53:59increase in the clinical clinically
• 54:00relevant non major bleeding and
• 54:03individuals who are getting doax
• 54:05for cancer associated thrombosis.
• 54:07So when when you prescribe either
• 54:09a low molecular weight heparin
• 54:10orado act to a patient with cancer
• 54:13associated thrombosis, how do you?
• 54:14How do you?
• 54:17Decide on the benefits, risks there,
• 54:19and what what agents do.
• 54:20You tend to choose and are there.
• 54:22Are there things about the
• 54:23patient that may point you
• 54:24in One Direction or another?
• 54:28So the clinically relevant non major
• 54:31bleeding was really of concern,
• 54:33which was higher in doax and
• 54:35that has been pretty consistent
• 54:37throughout all the six trials.
• 54:39So it wasn't just one study.
• 54:42And the way it impacts my practice
• 54:44is if if I do look at the patient's
• 54:47underlying bleeding risk.
• 54:49If there isn't an individual where I
• 54:51would be more concerned about bleeding,
• 54:53perhaps someone who had immediate
• 54:56postoperative thrombotic event,
• 54:58or perhaps with somebody who's going
• 55:00for a surgery or has a known history
• 55:03of underlying bleeding or faults.
• 55:05I might be more inclined to use
• 55:09those individuals rather than doax,
• 55:11so that would be my approach and.
• 55:13How I would use that information?
• 55:15Thank
• 55:15you very much, don't you?
• 55:17And Alex, are there any situations
• 55:20in patients with ITP, and in in,
• 55:22in which you might hold off on giving
• 55:26COVID vaccine COVID-19 vaccine?
• 55:28So individuals who are recently flared
• 55:30or have very low platelet counts and
• 55:34requiring intense therapy, for instance?
• 55:38You know, so this is interesting
• 55:40because the data they really didn't
• 55:42actually include specifically,
• 55:43like they didn't address the question
• 55:47of whether patients who were in right,
• 55:50right, or right now on inactive.
• 55:55ITP destinations,
• 55:57prior to prior to vaccination. They were.
• 56:00They only had patients who were on
• 56:02sort of chronic chronic therapy,
• 56:04so I I don't think we have data per
• 56:09say in that regard, but personally,
• 56:12I think if there's a flare actually flare,
• 56:17I probably would hold off,
• 56:20just not to disturb.
• 56:23You know it. You know,
• 56:25in in in response further,
• 56:28I think it would might what might be
• 56:31really interesting is in in this situation
• 56:33to address further whether they're truly.
• 56:36Uh and antibody platelet antibody,
• 56:39which none of them really looked into.
• 56:43Great, but but I think I would
• 56:45probably hold off until there's some
• 56:46stabilization of platelet count.
• 56:49Seems very prudent. Yep, OK, alright.
• 56:53Well it's it's just about 1:00 o'clock,
• 56:55so I want to thank our speakers for again.
• 56:58Excellent presentation that
• 57:00were informative and I think
• 57:02highlighted some really important
• 57:03areas in classical hematology.
• 57:05And thank you all for for joining us.
• 57:08Thank you very much.
• 57:09Have a great day everyone. I.