Complement Inhibition Using Eculizumab Overcomes Platelet Transfusion Refractoriness in Allo-Immunized Patients Receiving HLA Mismatched Platelets

Abstract Background: 30-50% of heavily platelet transfused patients will ultimately develop HLA allo-immunization. Although HLA-matched platelets can be lifesaving for these patients, a substantial proportion of patients receiving partially HLA-matched platelet products develop platelet transfusion refractoriness, putting them at risk for serious bleeding complications. Recent data suggest compliment activation leading to the destruction of platelets bound by HLA allo-antibodies may play a pathophysiologic role in platelet refractoriness. Eculizumab is a monoclonal antibody that binds and inhibits C5 compliment, blocking both the classic and alternative pathways of compliment. Here we investigated whether eculizumab treatment could be used to overcome platelet transfusion refractoriness in HLA allo-immunized patients. Methods: We conducted a one armed; phase II pilot trial (NCT02298933) in which HLA allo-immunized patients with platelet transfusion refractoriness received a single infusion of eculizumab at a dose of 1200mg. Eligible patients included adults age 18-75 with severe thrombocytopenia who had detectable HLA class I antibodies associated with platelet transfusion refractoriness (defined as a post-transfusion corrected count increment (CCI) of <7500/ul and <5000/ul at 10-60 mins and 18-24 hrs respectively that occurred following at least 2 consecutive platelet transfusions). Patients were defined to respond to therapy if one of the first 2 platelet transfusions following eculizumab infusion resulted in a CCI>7500/uL at 10-60 mins and CCI>5000/uL at 18-24 hrs post transfusion. Subjects were taken off study 14 days following eculizumab treatment. Responding patients who developed recurrent platelet refractoriness after planned study withdrawal were eligible to re-enroll on study. All patients were required meningococcal vaccination before eculizumab infusion +/- antibiotic prophylaxis to cover N. meningitidis. Results: As of 8/2016, 8 Eculizumab infusions were administered to 7 HLA allo-immunized subjects (median age 40 yrs, range 24-71) with severe thrombocytopenia associated with platelet transfusion refractoriness. Patients had an underlying diagnosis of SAA (n=3), refractory/relapsed AML (n=2; 1 patient had just finished conditioning for a haplo-identical transplant), relapsed ALL (n=1; post MUD transplant) and high risk MDS (n=1). Compliment, total (CH50) was the most reliable and consistent measure for complement inhibition. After Eculizumab infusion, CH50 decreased to <20U/ml in all treated patients. 3 of 8 (43%) patients had a response to therapy with platelet refractoriness resolving following 4/8 (50%) eculizumab administrations (Figures 1-3). Subject 1 received an additional 2nd treatment with eculizumab 2 months after her 1st response and again had resolution of platelet refractoriness (Figure 1A&1B). In 3 out of 4 cases where platelet refractoriness was overcome, the administered platelet product given immediately after eculizumab treatment expressed an HLA allele for which an HLA antibody had been detected in the patient's serum. Resolution of platelet refractoriness resulted in a clinically meaningful reduction in the requirement for platelet transfusions: the median number of platelet transfusion given 2 weeks before and 2 weeks after the eculizumab infusion in responding patients was 8.5 (range 3-10) and 4.5 (range 3-5) transfusions respectively. For the non-responders, the median number of platelet transfusions given 2 weeks before and 2 weeks after the eculizumab infusion was 8 (range 7-10 ) and 9.5 (range 6-15) transfusions respectively. Conclusions: The preliminary data from this ongoing trial suggest eculizumab may have efficacy in overcoming HLA antibody-associated platelet transfusion refractoriness. Remarkably, we observed eculizumab overcame platelet refractoriness in a subset of HLA allo-immunized patients receiving HLA mismatched platelet products that expressed an HLA allele for which an HLA antibody was detectable in the patient's serum. These data raise the possibility that eculizumab administration could be of therapeutic benefit in patients with platelet refractoriness as a consequence of newly discovered HLA antibodies, buying time for transfusion medicine departments to acquire HLA matched platelets or until platelet recovery occurs following chemotherapy or stem cell transplant. Disclosures No relevant conflicts of interest to declare.

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Severe Thrombocytopenia Does Not Increase Bleeding Complications in Patients Undergoing Bronchoscopy

Blood ◽

10.1182/blood.v124.21.4293.4293 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4293-4293

Author(s):

Lakshminarayanan Nandagopal ◽

Muthu Veeraputhiran ◽

Tania Jain ◽

Ayman Soubani ◽

Charles A. Schiffer

Keyword(s):

Platelet Count ◽

Renal Dysfunction ◽

Platelet Transfusion ◽

Conflicts Of Interest ◽

Bleeding Complications ◽

British Thoracic Society ◽

Severe Thrombocytopenia ◽

Platelet Counts ◽

Number Of Patients ◽

Platelet Transfusions

Abstract Introduction Prophylactic platelet transfusions are often performed prior to bronchoscopy or broncho-alveolar lavage (BAL) to prevent bleeding in thrombocytopenic patients. There is a paucity of data to validate this approach, with a platelet transfusion threshold of <50,000/mm3 largely based on expert opinion. We conducted a retrospective study on the incidence of bleeding complications in thrombocytopenic patients undergoing bronchoscopy. Methods We identified 150 consecutive patients with platelet counts <100,000/mm3 who underwent bronchoscopy and/or BAL from January 2009 to May 2014 at our institution. Bronchoscopies performed in patients with frank hemoptysis and trans-bronchial lung biopsy procedures were excluded. Patient characteristics, underlying diagnosis, platelet count prior to bronchoscopy, administration of platelet transfusions and bronchoscopy details were recorded. Factors affecting bleeding risk including presence of renal dysfunction (defined as BUN >30 and/or Cr>2.0) and coagulation studies (PT, PTT, INR) were identified. The British Thoracic Society guidelines1 were used to categorize bleeding as a result of bronchoscopy. Data were analyzed using descriptive statistics. Results The median age was 59 years (range 27-90), with two-thirds of patients (63%) being male. One hundred and seventeen (78%) patients had underlying malignancy and 55 (37%) had thrombocytopenia related to malignancy. Fellows and residents under the supervision of a bronchoscopy certified attending performed all but 4 of the bronchoscopies. Infection (40%) was the primary indication for bronchoscopy with BAL performed in 127 (85%) patients. Fifty-eight of 89 (65%) patients with baseline platelet counts <50,000/mm3 received prophylactic transfusions compared to 8% of those with platelet counts >50,000/mm3. The platelet count did not rise to >50,000//mm3 in many transfused patients. Seventy patients (47%) had counts <50,000/mm3 and eighty patients (53%) had counts >50,000/mm3 at the time of bronchoscopy. 49% were receiving immunosuppressive medications, 45% had renal dysfunction and 8% had INR >1.5. Bloody lavage that resolved spontaneously without continuous suctioning (Grade 0) was observed in 9 (6%) patients. Bleeding that required continuous suctioning but then resolved spontaneously (Grade 1) was noted in 1 patient with a platelet count of 61,000/mm3. Of 10 total bleeding events, 7 occurred in patients who were intubated. Two additional patients with platelet counts of 30,000/mm3 and 53,000/mm3 had diffuse alveolar hemorrhage, which was present before bronchoscopy. “Old” blood and blood clots were observed in 6 patients. Discussion The low incidence of bleeding complications from bronchoscopy +/- BAL even in patients with platelet counts <30,000/mm3 (3 episodes in 31 patients, all grade 0) demonstrates that bronchoscopy can be safely done in severely thrombocytopenic patients. Adopting a lower threshold for prophylactic transfusions could save a considerable number of platelet units and translate into significant cost savings and decreased risk of transfusion-related complications. Table 1 Platelet count, transfusion history and bleeding complications during bronchoscopy Platelet count at the time of bronchoscopy Number (n) and percentage (%) of patients who underwent bronchoscopy Number of patients who received prior platelet transfusion Bleeding during bronchoscopy n % 0-15,000/mm3 9 6% (9/150) 5 Grade 0=1 pt 16-29 22 15% 16 Grade 0=2 pts 30-39 17 11% 9 Grade 0=1 pt 40-49 22 15% 9 Grade 0=3 pts 50-75 44 29% 14 Grade 1=1 pt 76-100 36 24% 10 Grade 0=2 pts Total 150 63 Grade 0=9 pts, Grade 1=1 pt. 1.Du Rand IA, Blaikley J, Booton R, et al. British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults: accredited by NICE. Thorax. 2013:68 Suppl 1:i1-i44 Disclosures No relevant conflicts of interest to declare.

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Bloodless tandem autologous stem cell transplant for multiple myeloma in Jehovah's Witness patients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e19523 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e19523-e19523

Author(s):

Fnu Rafiullah ◽

Sarah L Mott ◽

Allyson Schultz ◽

Guido J. Tricot

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplant ◽

Pulmonary Hemorrhage ◽

Median Number ◽

Bleeding Complications ◽

Cell Transplant ◽

Blood Products ◽

Grade Iii ◽

Platelet Transfusions

e19523 Background:, Cases of Jehovah’s Witnesses (JW) who undergo, and survive, autologous and allogeneic stem cell transplant(SCT) are increasingly reported. Tandem autologous stem cell transplantation(ASCT) for multiple myeloma has not been previously reported in JW. We are describing the first reports of four JW patients who successfully underwent tandem bloodless ASCT for multiple myeloma. Methods:, We retrospectively studied the outcome of four JW patients who underwent tandem ASCT from November 2000 to January 2017. . The bleeding complications, number and cost of transfusion of blood products were compared with last 100 consecutive tandem autologous transplants done from November 2014 till January 2017. Results:,There were 4 JW patients and 59 non-JW patients. Among 4 JW patients 3 were male and 1 was female. Among 59 non-JW 24(40.7%) were female and 35 (59.3%) were female. Median age was 60-years (range 54–66) and 59-years (range 36–71) for JW and non-JW patients, respectively. At Day+30 one JW patient had grade III pulmonary hemorrhage and Non-JW patients had no grade III or higher bleeding problems .The median number of CD34 cells transfused was 7.48 millions cells/kg in non-JW patients while it was 9.44 millions/kg in JW patients. Complete Remission(CR) was achieved in 33(59%) after 1st tandem and 35(81.4%) after the second tandem transplant in Non-JW patients as compared to 100% CR rate in JW patients . The median number of platelet transfusions in non-JW patients was 2(range 0—21) and PRBC units was 1(range 0—7) at day+30 . Total cost of PRBC and platelet transfusions for the 59 non-JW patients was ~ 192,374 dollars (average 1923.74$/transplant). This excludes the supply costs and management of transfusion reactions costs. Conclusions: 1) Tandem autologous transplant for multiple myeloma in JW population is practical and largely safe. 2) Blood products are expensive and can be further minimized based on the JW patient data

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A Restrictive Platelet Transfusion Policy Allowing Long-Term Support of Outpatients With Severe Aplastic Anemia

Blood ◽

10.1182/blood.v93.9.3124 ◽

1999 ◽

Vol 93 (9) ◽

pp. 3124-3126 ◽

Cited By ~ 68

Author(s):

Markus Sagmeister ◽

Lic Oec ◽

Jürg Gmür

Keyword(s):

Aplastic Anemia ◽

Platelet Transfusion ◽

Severe Aplastic Anemia ◽

Bleeding Complications ◽

Outpatient Basis ◽

Platelet Counts ◽

The Mean ◽

Restrictive Policy ◽

Platelet Transfusions

Abstract The threshold for prophylactic platelet transfusions in patients with hypoplastic thrombopenia generally recommended in the standard literature is 20,000 platelets/μL. A more restrictive transfusion policy may be indicated in patients with chronic severe aplastic anemia (SAA) in need of long-term platelet support. We evaluated the feasibility and safety of a policy with low thresholds for prophylactic transfusions (≤5,000 platelets/μL in stable patients; 6,000 to 10,000 platelets/μL in cases with fever and/or hemorrhagic signs) combined with progressive lengthening of transfusion intervals (up to at least 7 days irrespective of the interim course of platelet counts). The study was based on a retrospective analysis of a total of 18,706 patient days with platelet counts ≤10,000/μL in patients with chronic SAA treated (for more than 3 months) on an outpatient basis. Altogether, 1,135 platelet transfusions were given, 88% at counts ≤10,000/μL and 57% at counts ≤5,000/μL. The mean transfusion interval was 10 days. During the period of observation, three major nonlethal bleeding complications occurred, which could be well controlled. We conclude that the restrictive policy with low transfusion thresholds and prolonged transfusion intervals proved feasible and safe in chronic SAA patients.

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How well do platelets prevent bleeding?

Hematology ◽

10.1182/hematology.2020000136 ◽

2020 ◽

Vol 2020 (1) ◽

pp. 518-522

Author(s):

Darrell J. Triulzi

Keyword(s):

Platelet Transfusion ◽

Anticoagulation Therapy ◽

Outpatient Setting ◽

Severe Thrombocytopenia ◽

Transfusion Threshold ◽

Spontaneous Bleeding ◽

Risk Of Bleeding ◽

Increased Risk ◽

High Incidence ◽

Platelet Transfusions

Abstract Prophylactic platelet transfusions are used to reduce the risk of spontaneous bleeding in patients with treatment- or disease-related severe thrombocytopenia. A prophylactic platelet-transfusion threshold of <10 × 103/µL has been shown to be safe in stable hematology/oncology patients. A higher threshold and/or larger or more frequent platelet doses may be appropriate for patients with clinical features associated with an increased risk of bleeding such as high fevers, sepsis, disseminated intravascular coagulation, anticoagulation therapy, or splenomegaly. Unique factors in the outpatient setting may support the use of a higher platelet-transfusion threshold and/or dose of platelets. A prophylactic platelet-transfusion strategy has been shown to be associated with a lower risk of bleeding compared with no prophylaxis in adult patients receiving chemotherapy but not for autologous transplant recipients. Despite the use of prophylactic platelet transfusions, a high incidence (50% to 70%) of spontaneous bleeding remains. Using a higher threshold or larger doses of platelets does not change this risk. New approaches to reduce the risk of spontaneous bleeding, including antifibrinolytic therapy, are currently under study.

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Routine Prophylactic Platelet Transfusions Are Not Necessary for Patients in Clinically Stable Condition after Autologous Peripheral Stem Cell Transplantation(ASCT): Updated Results in 106 Patients.

Blood ◽

10.1182/blood.v104.11.3636.3636 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3636-3636

Author(s):

Kerstin Schaefer-Eckart ◽

Markus Frank ◽

Martin Wilhelm ◽

Hannes Wandt

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Platelet Count ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Platelet Transfusion ◽

Median Number ◽

Peripheral Stem Cell Transplantation ◽

New Strategy ◽

Platelet Transfusions

Abstract We present our extended experience with an only therapeutic platelet transfusion strategy in patients after autologous peripheral stem cell transplantation(ASCT). Clinically stable patients(fever < 38,5°Celsius, no local infections, no sepsis syndrome) received single donor apheresis platelet transfusions only in the case of bleeding WHO ≥ II°, while prophylactic platelet transfusions were given to clinically instable patients if the morning platelet count was < 10/nl. In a first analysis after 50 patients we have shown that this strategy was safe, with no bleeding greater than WHO II°. In a retrospective matched-pair analysis the total number of platelet units transfused was reduced to 50% compared to our former strategy with routine platelet transfusions given when the morning platelet count was below 10/nl. (ASH 2002). We now analysed 106 patients with a total number of 140 ASCTs. Median age was 54 years(19–70): The diagnoses were acute leukemia(17), lymphoma(34), solid tumors(9) and multiple myeloma(46). The conditioning regimens corresponded to standard protocols. Median days of thrombocytopenia < 20/nl and 10/nl were 6(0–92) and 3(0–62) respectively, with a total number of days with thrombocytopenia <20/nl and <10/nl of 989 and 508. Hemorrhages WHO I° and II° was observed in only 49 out of 140(35%) ASCTs. We observed no bleeding greater than WHO II°. The median number of platelet units was 1(0–18). 48 out of 140(34%) transplantations could be performed without platelet transfusions. In multiple myeloma this percentage was even higher: 32/68(47%). The indications for prophylactic transfusions were mainly FUO(21/61 – 34%) and mucositis with or without fever(19/61–31%). Considering age below or above the median age of 54 years or different diagnoses, there was no difference in days with platelets <10/nl, <20/nl, bleeding complications or median number of platelet units transfused. The total number of 234 transfusions in these 140 transplantations could have been even further reduced, because 15%(36/234) of the transfusions were given without a clear indication regarding the study regimen, because of a learning effect with this new strategy. This new strategy has shown to be very safe and prophylactic platetelet tansfusions are probably not necessary in clinically stable patients with fever as the only sign of an infection. We are just starting a multicenter randomised study comparing this new strategy with the former strategy of routine prophylactic platelet transfusion.

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A Multi-Centre Prospective Observational Study of Platelet Transfusion Practice in Neonates with Severe Thrombocytopenia.

Blood ◽

10.1182/blood.v108.11.961.961 ◽

2006 ◽

Vol 108 (11) ◽

pp. 961-961 ◽

Cited By ~ 4

Author(s):

Neil Murray ◽

Sally Ballard ◽

Angela Casbard ◽

Mike Murphy ◽

Irene Roberts ◽

...

Keyword(s):

Observational Study ◽

Major Bleeding ◽

Platelet Transfusion ◽

Transfusion Practice ◽

Major Haemorrhage ◽

Study Entry ◽

Severe Thrombocytopenia ◽

Minor Bleeding ◽

Grade 3 ◽

Platelet Transfusions

Abstract Background: Platelet transfusion practice in neonates is not evidence-based and there is a lack of data relating transfusion to clinical outcome. To inform the design of clinical trials, we conducted a prospective multicentre observational study of platelet transfusion in thombocytopenic neonates to describe: transfusion practice, including reason for transfusion; clinically-related outcomes, including minor and major bleeding and mortality. Methods: Neonates with platelets <60x109/l were studied at 7 UK neonatal intensive care units Mar 05-Jun 06. With parental consent, daily data were collected on minor bleeding (blood staining of oral/nasogastric/endotracheal secretions and stool; microscopic haematuria; petechial rash; oozing from puncture sites - scored 0–7), and major bleeding (intraventricular (IVH), intra-abdominal, pulmonary or renal). Surviving neonates were studied for 7 days or until platelets were ≥60x109/l. Blood counts and all transfusions were directed by the attending neonatologist, with reason for transfusion and its effect on bleeding prospectively documented. Results: 145 of 167 (87%) eligible neonates were enrolled; 123 (85%) were < 37 weeks gestational age (GA), 89 (61%) were male. The study documented 186 episodes of thrombocytopenia (1606 study days) and 309 platelet transfusions given to 91 (63%) neonates. GA, birth weight and age at thrombocytopenic episode were: 27 (24–32) weeks; 825 (675–1370) grams; 5 (2–16) days, respectively [all data median (IQR)]. 21/145 babies (14%) had major IVH (Grade 3/4) at study entry. Platelets (x 109/l) at study entry, and at platelet nadir, and duration of count <60x109/l were: 44 (33–54); 31 (19–42); 2 (1–5) days respectively. In transfused neonates, platelets (x109/l) pre- and post-transfusion, and number of transfusions were: 27 (19–36); 84 (46–138); 2 (1–4) respectively. The principal indications for transfusion were:- platelet count below threshold of unit guideline: 265/309 (86%); deteriorating clinical condition: 17/309 (6%); and significant bleeding: 7/309 (2%). At least 1 episode of minor bleeding was recorded on 622/1606 (39%) of study days. Minor bleeding scores recorded for 12 hours pre- and post each transfusion were [median (IQR)]: 1 (0–2) and 0 (0–1) respectively. New or extension of IVH bleeding to Grade 3/4 occurred in 7 neonates and other major haemorrhage in 9 neonates (4 pulmonary, 3 GI). A total of 20/145 (14%) neonates died, 13 with major IVH bleeding (of which 10 had Grade 3/4 IVH at study entry); all received platelet transfusions [total 87; median 3 (2 to 7). Conclusion: This study confirms that most neonates with severe thrombocytopenia are preterm, most episodes develop after 72 hours of life (median 5 days) and are of short duration (median 2 days). Minor haemorrhage is common and may be reduced by platelet transfusion. Major haemorrhage is uncommon (11%), is associated with mortality (82%) and affected patients receive a large number of platelet transfusions. There is a clear distinction between the majority of thrombocytopenic neonates who receive one or two transfusions as prophylaxis with a good outcome, and the minority who suffer adverse outcomes despite transfusion. Many neonates are transfused with platelets at thresholds below those suggested in guidelines without apparent clinical detriment. These data will be invaluable for planning the randomised trials necessary for rationalising platelet transfusion in these vulnerable patients.

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The Use Of Simple Patient Blood Management Strategies As An Alternative To Platelet and Red Cell Transfusion In Autologous Stem Cell Transplant

Blood ◽

10.1182/blood.v122.21.2140.2140 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2140-2140

Author(s):

Patricia A. Locantore-Ford ◽

Shakira Jeanene Grant ◽

Gina Keck

Keyword(s):

Stem Cell Transplant ◽

Median Number ◽

Autologous Stem Cell Transplant ◽

Bleeding Complications ◽

Cell Transplant ◽

Red Cell ◽

Blood Management ◽

Transplant Patients ◽

Iv Iron ◽

Red Cell Transfusion

Abstract Introduction High dose chemotherapy (HDC) followed by autologous stem cell transplant (ASCT) is considered the standard of care for patients with high-risk or relapsed lymphoma and multiple myeloma (MM). With most patients requiring both red cell transfusion ,and platelet support until marrow engraftment. Jehovah’s Witnesses (JW), based on religious convictions, refuse blood products, and therefore are frequently denied transplants in most centers, due to the presumed fear of death from bleeding and anemia. We present a series of 119 JW diagnosed with lymphoma (n= 54), (MM) (n= 63) and amyloidosis (n=2) who received treatment with HDC and ASCT without transfusion support. Methods All JW undergoing HDC and ASCT at Pennsylvania Hospital between May 1996 and March 2013 were included. Patients were primed pre-transplant with IV iron and erythropoietin to a target Hemoglobin (Hb) > 11g/dl.Cryopreservation of collected cells, was performed using normal saline and albumin instead of fresh frozen plasma. Post apheresis, HDC was delayed to allow Hb levels to rise to ≥ 11 g/dl and platelets ≥100,000. Post-transplant, patients received granulocyte colony-stimulating factor, erythropoietin and initially interleukin-11 which was later discontinued, as there was no benefit observed in the length of time to platelet engraftment. Thrombocytopenia was managed with antifibrinolytic agents (Amicar) and vitamin K, the avoidance of anticoagulation and aspirin, and rarely cryoprecipitate, desmopressin, and nasal vasoconstrictors. Results Engraftment The median number of days to neutrophil engraftment, with absolute neutrophil count ≥1,000/μL, was 10.0 days. The median Hb at the onset of chemotherapy was 11.8 g/dL, (range 7-15.3 g/dL), and the average decrease in Hb was 5.0 g/dL, with an average nadir of 6.8 g/dL. The median number of days with Hb under 8 g/dL was 5.5 days. The median platelet count at onset of chemotherapy was 148 x 103/μL (range of 65 to 502 x 103/μL). The median number of days with a platelet count under 10 x 103/μL was 3.0 days (range 0 to 14 days) with a median platelet nadir of 4.0 x 103/μL (range 1-50 x 103/μL). Patients with lymphoma experienced a lower drop in Hb post cytotoxic regimen than myeloma patients (ΔHb = 4.5g/dl for MM, 6.0g/dl for lymphoma, p < 0.05).The average length of stay (LOS) was 19.0 days. Bleeding Complications Bleeding complications were classified using the WHO criteria. Patients with platelet counts greater than 5 x 103/μl experienced no bleeding complications or death due to hemorrhage. There was one grade 4 hemorrhage, a temporal infarct leading to temporary vision loss and confusion, one grade 3 hemorrhage, a major gastrointestinal bleed, and one grade 2 hemorrhage which was hematuria. Sixteen patients experienced grade 1 bleeding episodes consisting of subconjunctival hemorrhage (n=5), epistaxis (n=6), minor vaginal bleeding (n=2), minor oral bleeding (n=1) a thigh hematoma (n=1), and a minor retinal bleed (n=1). Cardiac Complications Forty two of the one hundred and nineteen patients who underwent HDC and ASCT, experienced cardiac complications.These included new onset arrhythmias (n=19), profound hypotension (n=15), congestive heart failure (n=10) and acute myocardial infarction (n=1). The mean Hb nadir for patients who experienced a cardiac complication was 6.6 g/dL .Additionally the median age was 56 years (range 21-71years) and the average change in hemoglobin was 5.0g/dl. Mortality The 100 day transplant related mortality was 5%.The six deaths recorded were due to sepsis, multi-organ failure due to pancytopenia and cardiac events. Conclusion Based on our study we conclude that HDC followed by ASCT, can safely be performed without the need for transfusion support, with low mortality rates and low incidences of major bleeding complications .Anticipated anemia may be managed by ensuring priming of Hb with the use of IV iron and erythropoietin to Hb ≥11 g/dl, and simple patient blood management techniques. Thrombocytopenia may be managed similarly, by allowing platelet recovery post apheresis to ≥ 100, 000. We also believe that Amicar and Vitamin K offer as good and effective, an alternative to prophylactic platelet transfusion in the management of thrombocytopenia. Additionally these agents may be used to achieve homeostasis in patients who develop platelet refractoriness, and similarly the use in all transplant patients may be appropriate. Disclosures: No relevant conflicts of interest to declare.

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Evaluation of four methods for platelet compatibility testing

Blood ◽

10.1182/blood.v69.5.1425.bloodjournal6951425 ◽

1987 ◽

Vol 69 (5) ◽

pp. 1425-1430

Author(s):

JG McFarland ◽

RH Aster

Keyword(s):

Platelet Transfusion ◽

Statistical Significance ◽

51Cr Release ◽

Hla Antibodies ◽

Platelet Suspension ◽

Platelet Recovery ◽

Single Donor ◽

Hla Compatibility ◽

Matched Donor ◽

Platelet Transfusions

Four platelet compatibility assays were performed on serum and platelet or lymphocyte samples from 38 closely HLA-matched donor/recipient pairs involved in 55 single-donor platelet transfusions. The 22 patients studied were refractory to transfusions of pooled random-donor platelets. Of the four assays (platelet suspension immunofluorescence, PSIFT; 51Cr release; microlymphocytotoxicity; and a monoclonal anti-IgG assay, MAIA), the MAIA was most predictive of platelet transfusion outcome (predictability, 74% for one-hour posttransfusion platelet recovery and 76% for 24-hour recovery). The only other assay to reach statistical significance was the PSIFT (63% predictability for one-hour posttransfusion recovery). The degree of HLA compatibility between donor and recipient (exact matches v those utilizing cross-reactive associations) was unrelated to the ability of the MAIA to predict transfusion results. The MAIA may be capable of differentiating HLA antibodies, ABO antibodies, and platelet-specific antibodies responsible for failure of HLA-matched and selectively mismatched single-donor platelet transfusions.

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The Burden of Clinically Significant Bleeding, Thrombocytopenia and Platelet Transfusions in Myelodysplastic Syndromes

Blood ◽

10.1182/blood-2019-125273 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 719-719

Author(s):

Kathleen Pao Lynn Cheok ◽

Rakchha Chhetri ◽

Li Yan A Wee ◽

Arabelle Salvi ◽

Simon McRae ◽

...

Keyword(s):

Risk Factors ◽

Antiplatelet Therapy ◽

Myelodysplastic Syndromes ◽

Cumulative Incidence ◽

Platelet Transfusion ◽

Severe Thrombocytopenia ◽

Bleeding Events ◽

Platelet Counts ◽

Immune Mediated ◽

Platelet Transfusions

Aim: Although 40-65% of myelodysplastic syndromes (MDS) patients are thrombocytopenic and require platelet transfusions, there is limited literature on the risk factors predictive of bleeding and the burden of immune mediated platelet refractoriness (PLT-R). Objectives: To evaluate the prevalence of thrombocytopenia, incidence of bleeding events, platelet transfusion dependency (PLT-TD) and immune-mediated platelet refractoriness (PLT-R) in MDS patients. Methods: A retrospective analysis of 754 MDS patients enrolled in the South Australian MDS (SA-MDS) registry was performed. Platelet counts <100, <50 and <20 (x109/L) were used to define mild, moderate and severe thrombocytopenia respectively. The severity of bleeding events was classified according to the International Society of Thrombosis and Haemostasis (ISTH) classification. PLT-TD was defined as transfusion of at least one unit of platelets each month for four consecutive months. All other patients were classified as transfusion independent (PLT-TI). Immune mediated PLT-R was defined if a patient had HLA-class I or HPA antibodies, poor platelet increments and required HLA-matched platelets. Medication history with regards to anticoagulation and/or antiplatelet therapy was also collected. Results: At diagnosis, 332 (45%) patients had thrombocytopenia and 106 (14%) patients had moderate to severe thrombocytopenia. During the study period, 249 bleeding events were recorded in 162 (21%) patients with a cumulative incidence of 33% (Fig 1A). Of the 249 bleeding events, 85 (34%) were major and 164 (66%) were clinically relevant minor bleeding. Notably, 16, 90 and 5 bleeding events were intracranial, gastrointestinal, intraocular respectively. While 41% (96/235) bleeding events occurred in the setting of moderate to severe thrombocytopenia, 21% and 38% (Fig 1B) of bleeding events occurred at platelet counts of >50-100 and >100x109/L respectively. Twenty-eight percent (69/249) bleeding events were associated with concomitant anticoagulation and/or antiplatelet therapy and importantly, platelets counts were >50x109/L and >100 x109/L in 57 (83%) and 46 (67%) at the time of bleeding events, respectively. During the disease course, 393 (52%) patients required at least one unit of platelet transfusion. 106 (14%) patients were PLT-TD and had significantly poor overall survival (OS) compared to PLT-TI (26 vs 42 months, p<0.0001). In total, 30/393 (7%) required HLA-matched platelet transfusions. 20/30 (66%) of PLT-R patients were female receiving disease modifying therapy (DMT). This was substantiated by cox regression analysis, demonstrating that females (HR=5.32, p=0.0006), older age (HR=0.97, p=0.028) and haemoglobin (Hb) at diagnosis (HR=1.03, p=0.009) were independent risk factors for PLT-R. Importantly, 20/76 (25%) female patients receiving platelets and DMT developed immune mediated PLT-R requiring HLA matched platelets. Conclusions: In our cohort of MDS patients, cumulative incidence of bleeding is 33% and 59% of the bleeding events occurred at platelet counts >50X109/L. For all bleeding events that occurred while on anticoagulation and/or antiplatelet therapy, 83% events occurred with platelet counts >50 x 109/L. Therefore, guidelines for anticoagulation and/or antiplatelet therapy are required for MDS patients. We also showed that development of PLT-TD is associated with poor OS. Importantly, 1 in 4 female MDS patients receiving platelets and DMT required HLA-matched platelets. Platelet transfusions practices should be optimised for these high-risk groups. Disclosures No relevant conflicts of interest to declare.

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A Multicenter Study of Platelet Recovery and Utilization in Patients After Myeloablative Therapy and Hematopoietic Stem Cell Transplantation

Blood ◽

10.1182/blood.v91.9.3509.3509_3509_3517 ◽

1998 ◽

Vol 91 (9) ◽

pp. 3509-3517 ◽

Cited By ~ 2

Author(s):

Steven H. Bernstein ◽

Auayporn P. Nademanee ◽

Julie M. Vose ◽

Guido Tricot ◽

Joseph W. Fay ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Platelet Transfusion ◽

The United States ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Platelet Recovery ◽

Clinical Variables ◽

Hemorrhagic Event

An observational study was conducted at 18 transplant centers in the United States and Canada to characterize the platelet recovery of patients receiving myeloablative therapy and stem cell transplantation and to determine the clinical variables influencing recovery, determine platelet utilization and cost, and incidence of hemorrhagic events. The study included 789 evaluable patients transplanted in 1995. Clinical, laboratory, and outcome data were obtained from the medical records. Variables associated with accelerated recovery in multivariate models included (1) higher CD34 count; (2) higher platelet count at the start of myeloablative therapy; (3) graft from an HLA-identical sibling donor; and (4) prior stem cell transplant. Variables associated with delayed recovery were (1) prior radiation therapy; (2) posttransplant fever; (3) hepatic veno-occlusive disease; and (4) use of posttransplant growth factors. Disease type also influenced recovery. Recipients of peripheral blood stem cells (PBSC) had faster recovery and fewer platelet transfusion days than recipients of bone marrow (BM). The estimated average 60-day platelet transfusion cost per patient was $4,000 for autologous PBSC and $11,000 for allogeneic BM transplants. It was found that 11% of all patients had a significant hemorrhagic event during the first 60 days posttransplant, contributing to death in 2% of patients. In conclusion, clinical variables influencing platelet recovery should be considered in the design and interpretation of clinical strategies to accelerate recovery. Enhancing platelet recovery is not likely to have a significant impact on 60-day mortality but could significantly decrease health care costs and potentially improve patient quality of life.

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