Caplacizumab for treatment of thrombotic thrombocytopenic purpura in a patient with anaphylaxis to fresh-frozen plasma.

BACKGROUND: Plasma exchange with plasma replacement has been the mainstay for the treatment of thrombotic thrombocytopenic purpura (TTP) for several decades. Recently an anti-von Willebrand factor (VWF) medication, caplacizumab, has been approved for treatment of TTP when used with plasma exchange. We report a patient with immune-mediated TTP that had an anaphylactic reaction to plasma who was then given caplacizumab daily for 1 week without further plasma exchange therapy with a good clinical and laboratory response. CASE REPORT: A 63-year-old woman with acute confusion and multiple ecchymoses after tooth extraction developed TTP with a hemoglobin (Hb) of 6.3 g/dL, white blood cell count 15 × 109 /L, platelets (PLTs) 12 × 109 /L, lactate dehydrogenase (LDH) 1212 IU/mL, and creatinine 0.9 mg/dL. Her ADAMTS13 level was less than 5% and plasma exchange was started. During the first plasma exchange the patient developed anaphylaxis with hypotension, shortness of breath, angioedema, and urticaria. She recovered from this reaction with treatment and no further plasma exchanges were performed. Instead she was given methylprednisolone, caplacizumab, and later rituximab. The caplacizumab was given daily for 8 days during which her PLT counts and ADAMTS13 levels improved. Her Hb level also increased. She continued to receive oral prednisone and rituximab after discharge was doing well latest follow up (Day 114). CONCLUSION: Caplacizumab may be used safely and effectively without concomitant plasma exchange in a patient with anaphylaxis to plasma.

Risk of hypotensive reactions is increased when using partial saline replacement for therapeutic plasma exchange.

BACKGROUND: Partial normal saline replacement during plasma exchange procedures is a common practice to reduce procedure costs but may increase the risk of adverse events, such as hypotension and citrate reactions. The goal of this study was to compare adverse event rates for the patients that used albumin or albumin/saline as replacement. STUDY DESIGN AND METHODS: A retrospective chart review was done of plasma exchange procedures that used all albumin or 80% albumin to 20% normal saline (80/20) as replacement. The procedure type (all albumin vs 80/20), the percent of normal saline used, age, gender, and adverse events during the procedure were recorded. RESULTS: During the study period, 3624 procedures were documented for 401 patients (46% female), age range 0 to 93 years, of which 2453 (67.7%) used 80/20. Overall 91 procedures (2.5%) resulted in a hypotensive event, 26 (0.7%) of which were classified as moderate to severe hypotension, and 40 (1.1%) had reported citrate toxicity. After adjusting for age, gender, and diagnosis using a generalized linear mixed model and backward model selection, results showed that 100% albumin had a significantly lower risk of having hypotension than 80/20 (odds ratio (OR): 0.531 [0.298, 0.946], P = 0.032) and moderate to severe hypotension (odds ratio: 0.140 [95% confidence interval (CI): 0.031, 0.628], P = 0.010). Older age was also predictive of having hypotensive reactions (OR[95%CI] = 1.017,[1.0, 1.034], P = 0.047). CONCLUSION: Partial saline use as a replacement fluid with albumin during plasma exchange is associated with an increased risk of hypotension. Use of saline as replacement fluid during plasma exchange should be minimized especially in older patients.

A Platelet Factor 4-Dependent Platelet Activation Assay Facilitates Early Detection of Pathogenic Heparin-Induced Thrombocytopenia Antibodies.

Heparin-induced thrombocytopenia (HIT) is a dangerous complication of heparin therapy. HIT diagnosis is established by recognizing thrombocytopenia and/or thrombosis in an affected patient and from the results of serological tests such as the platelet factor 4 (PF4)/heparin immunoassay (PF4 ELISA) and serotonin release assay (SRA). Recent studies suggest that HIT antibodies activate platelets by recognizing PF4 in a complex with platelet glycosaminoglycans (and/or polyphosphates) and that an assay based on this principle, the PF4-dependent P-selectin expression assay (PEA), may be even more accurate than the SRA for HIT diagnosis. Here, we demonstrate that the PEA detected pathogenic antibodies before the SRA became positive in two patients with HIT studied serially, in one case even before seropositivity in the PF4 ELISA. In one of the patients treated with plasma exchange, persistent dissociation between the PEA and SRA test results was observed. These results support a role for the PEA in early HIT diagnosis.

IVIg for Treatment of Severe Refractory Heparin-Induced Thrombocytopenia.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) complicated by severe thrombocytopenia and thrombosis can pose significant treatment challenges. Use of alternative anticoagulants in this setting may increase bleeding risks, especially in patients who have a protracted disease course. Additional therapies are lacking in this severely affected patient population. METHODS: We describe three patients with HIT who had severe thromboembolism and prolonged thrombocytopenia refractory to standard treatment but who achieved an immediate and sustained response to IVIg therapy. The mechanism of action of IVIg was evaluated in these patients and in five additional patients with severe HIT. The impact of a common polymorphism (H/R 131) in the platelet IgG receptor FcγRIIa on IVIg-mediated inhibition of platelet activation was also examined. RESULTS: At levels attained in vivo, IVIg inhibits HIT antibody-mediated platelet activation. The constant domain of IgG (Fc) but not the antigen-binding portion (Fab) is required for this effect. Consistent with this finding, IVIg had no effect on HIT antibody binding in a solid-phase HIT immunoassay (platelet factor 4 enzyme-linked immunoassay). The H/R131 polymorphism in FcγRIIa influences the susceptibility of platelets to IVIg treatment, with the HH131 genotype being most susceptible to IVIg-mediated inhibition of antibody-induced activation. However, at high doses of IVIg, activation of platelets of all FcγRIIa genotypes was significantly inhibited. All three patients did well on long-term anticoagulation therapy with direct oral anticoagulants. CONCLUSIONS: These studies suggest that IVIg treatment should be considered in patients with HIT who have severe disease that is refractory to standard therapies.

Red cell exchange to mitigate a delayed hemolytic transfusion reaction in a patient transfused with incompatible red blood cells.

PURPOSE: A red cell exchange was performed to prevent a potentially fatal hemolytic transfusion reaction in a patient with anti-e who was transfused with e-antigen unscreened red blood cells during liver transplant surgery. CASE REPORT: A 64-year-old woman with cirrhosis due to hepatitis C was scheduled to receive a liver transplant. She had a previously documented anti-e, an antibody to the Rh(e)-antigen that is known to cause delayed hemolytic transfusion reactions. Pre-operatively and intra-operatively, she had massive hemorrhage which required transfusion of 34 e-antigen unscreened red blood cells (RBCs) most of which were incompatible. The hemoglobin dropped from 9.1 g/dL on post-operative day (POD)1 to 6.6 g/dL on POD6, with no evidence of blood loss. The bilirubin also increased from 5.0 mg/dL on POD 1 to 11.0 mg/dL on POD 6. As she was also becoming more hemodynamically unstable, a red cell exchange with 10 units of e-negative RBCs was performed on POD 6. She improved clinically and was extubated the following day. A few residual transfused e-positive red cells were detected after the red cell exchange until POD 13. CONCLUSION: This case illustrates how a red cell exchange can mitigate the potentially harmful effects of a delayed hemolytic transfusion reaction caused by red cell antibodies. With massive intraoperative blood loss it may not be possible to have antigen-negative RBCs immediately available, particularly for the e-antigen, which is present in 98% of the donor population. The ability to perform such a procedure may be life-saving in such patients. J. Clin. Apheresis 32:59-61, 2017. © 2016 Wiley Periodicals, Inc.

Red cell storage age policy for patients with sickle cell disease: A survey of transfusion service directors in the United States.

In patients with sickle cell disease (SCD), the effects of the red cell storage lesion are not well defined. The objective of this study was to determine the prevalence of transfusion services that limit red cell units by storage age for patients with SCD. We developed a 22 question survey of transfusion service director opinions and their corresponding blood bank policies. Target subjects were systematically identified on the AABB website. Responses were recorded in SurveyMonkey and summarized using standard statistical techniques. Ninety transfusion service directors responded to the survey. Response rate was 22%. Only 23% of respondents had storage age policies in place for patients with SCD, even though 36% of respondents consider older units to be potentially harmful in this patient population. Of those with a policy, a less-than 15 day storage age requirement was most often used (75%), but practices varied, and most respondents (65%) agreed that evidence-based guidelines regarding storage age are needed for patients with SCD. Policies, practices and opinions about the risks of older units for patients with SCD vary. As patients with SCD may have unique susceptibilities to features of the red cell storage lesion, prospective studies in this population are needed to determine best practice.

Acute hemolytic transfusion reaction due to anti-Le(b).

BACKGROUND: Anti-Le(b) is usually a clinically insignificant antibody of immunoglobulin M subclass most often found in the sera of pregnant women or individuals that are Le(a-b-). We report a case of an acute hemolytic transfusion reaction due to a hemolytic anti-Le(b) that was not seen in the pretransfusion antibody detection test, but was strongly reactive in posttransfusion testing. CASE REPORT: A 30-year-old African-American woman with metastatic renal cell carcinoma was receiving chemotherapy. She was anemic with hemoglobin (Hb) of 7.2 g/dL and had a negative antibody detection test by the solid-phase red blood cell adherence method. She was transfused with 2 RBC units without incident. Nine days later her Hb was 7.9 g/dL again with a negative antibody detection test. Transfusion of an additional RBC unit was begun. During the transfusion she developed chills, nausea, hypertension, and red-brown urine. The posttransfusion sample plasma was grossly hemolyzed with a strongly positive direct antiglobulin test (DAT) by gel. By comparison the pretransfusion plasma was normal appearing and the DAT was weaker. The eluate was negative on both occasions. Anti-Le(b) was detected in the posttransfusion sample by MTS gel (Ortho Diagnostics). Both RBC units she had received before the RBC unit that caused the reaction were Le(b+) as was the implicated RBC unit. CONCLUSION: This case illustrates that anti-Le(b) which is usually clinically insignificant can occasionally cause severe hemolytic transfusion reactions. Only three other reported cases of anti-Le(b) causing hemolytic transfusion reactions could be found in the literature, two of which were in abstract form only.

Hemolytic transfusion reaction due to anti-IH.

BACKGROUND: Anti-IH is usually a clinically insignificant antibody that may complicate a serologic workup. However, it can occasionally cause hemolysis. We report a rare case of acute hemolysis caused by anti-IH. CASE REPORT: A 60-year-old man with a long history of chronic myelomonocytic leukemia and anemia, blood group A, D+ was found to have an unidentified antibody on serologic workup. He received an A, D+ red blood cell (RBC) unit that was crossmatch compatible by immunoglobulin G indirect antiglobulin test and then experienced an acute hemolytic transfusion reaction with fever, hemoglobinuria, and acute renal failure. The antibody was later identified as an anti-IH with a wide thermal amplitude. The transfused RBCs were later typed as A(2). The patient was subsequently typed as an A(1) individual. The patient recovered completely from the effects of this reaction and was transfused with A(1) RBCs over the next few days with no adverse effect. CONCLUSION: Anti-IH, which is usually clinically insignificant and often found in A(1), B, and A(1) B individuals, can, on rare occasions, cause acute hemolytic transfusion reactions, especially when an A(2) unit is transfused to an A(1) patient.

Hematologic malignancies in pregnancy.

Hematologic malignancies complicating pregnancy are uncommon, but a delay in diagnosis or treatment can mean the difference between life and death. It is the responsibility of the obstetrician, nurse-midwife, or nurse practitioner to maintain a high index of suspicion when patients present with unexplained lymphadenopathy or protracted constitutional symptoms. Management of these patients requires a multifaceted team from the oncology, pediatrics, and obstetrics services. With most hematologic cancers now requiring multiagent chemotherapy for optimal survival, the patient, her family, and her physicians are often faced with what seems to be a Faustian dilemma. Most infants exposed in utero to multiagent chemotherapy, however, seem to suffer no long-term detrimental consequences.