Initial US tertiary health care system experience using caplacizumab in patients with immune thrombotic thrombocytopenic purpura.

Several international registries have reported on the efficacy of caplacizumab for the treatment of immune thrombotic thrombocytopenic purpura (iTTP). Similar real-world data from the United States (US) are limited. In this single center retrospective study, we sought to describe caplacizumab prescribing patterns and review clinical outcomes for US patients with iTTP. Subjects were eligible for inclusion if they were diagnosed with acute iTTP and received care at University of Pittsburgh Medical Center-affiliated hospitals from 2012 to 2022. Subjects were divided into an historical cohort who received standard of care therapy alone, and early and late administration cohorts (EA and LA) who received caplacizumab within and greater than 72 h of admission, respectively, plus standard of care. Clinical data were collected from the electronic record. Thirty-two subjects were included: 16 historical, 12 EA, and 4 LA subjects. Refractoriness occurred more frequently in the LA and historical cohorts as compared to the EA cohort (4 (100%) vs. 6 (38%) vs. 3 (25%), p = 0.02). The LA cohort also experienced longer lengths of hospital stay, required more TPE procedures, and were exposed to the greatest amount of donor plasma (p < 0.05 for all) as compared to the other cohorts. Time to platelet count normalization was longest in the LA cohort (p = 0.013). There were no significant between-group differences in bleeding events. Because we are unable to predict which patients will develop refractoriness, we recommend frontline administration of caplacizumab to all patients with iTTP.

Successful management of maternal anti-PP1Pk alloimmunization in pregnancy with therapeutic plasma exchange and intravenous immunoglobulin.

Anti-PP1PK alloimmunization is rare given ubiquitous P1PK expression. Prevention of recurrent miscarriages and hemolytic disease of the fetus and newborn (HDFN) in pregnant individuals with anti-PP1PK antibodies has relied upon individual reports. Here, we demonstrate the successful management of maternal anti-PP1PK alloimmunization in a 23-year-old, G2P0010, with therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and monitoring of anti-PP1Pk titers. Twice-weekly TPE (1.5 plasma volume [PV], 5% albumin replacement) with weekly titers and IVIG (1 g/kg) was initiated at 9 weeks of gestation (WG). The threshold titer was ≥16. Weekly middle cerebral artery-peak systolic velocities (MCA-PSV) for fetal anemia monitoring was initiated at 16 WG. PVs were adjusted throughout pregnancy based on treatment schedule, titers, and available albumin. Antigen-negative, ABO-compatible RBCs were obtained through the rare donor program and directed donation. An autologous blood autotransfusion system was reserved for delivery. Titers decreased from 128 to 8 by 10 WG. MCA-PSV remained stable. At 24 WG, TPE decreased to once weekly. After titers increased to 32, twice-weekly TPE resumed at 27 WG. Induction of labor was scheduled at 38 WG. Vaginal delivery of a 2950 g neonate (APGAR score: 9, 9) occurred without complication (Cord blood: 1+ IgG DAT; Anti-PP1Pk eluted). Newborn hemoglobin and bilirubin were unremarkable. Discharge occurred postpartum day 2. Anti-PP1Pk alloimmunization is rare but associated with recurrent miscarriages and HDFN. With multidisciplinary care, a successful pregnancy is possible with IVIG and TPE adjusted to PV and titers. We also propose a patient registry and comprehensive management plan.

Effective peripheral blood stem cell collection in a 4.6-kg child.

BACKGROUND: Due to unique technical challenges, effective peripheral blood stem cell collections (PBSCs) have not been consistently reported in patients weighing less than 5 kg. We describe three PBSCs performed in a 4.6-kg child undergoing myeloablative chemotherapy for high-grade glioma. STUDY DESIGN AND METHODS: A multidisciplinary group representing the clinical and apheresis teams adapted a PBSC protocol to accommodate the patient's size and collection targets. Special considerations included timing of the collection relative to chemotherapy, vascular access, strategies for monitoring adverse events during collection, and contingencies. RESULTS AND DISCUSSION: The patient underwent three PBSC procedures over 2 days due to suboptimal collection after the first two procedures. For procedure 1, a conservative inlet: anticoagulant (AC) ratio and AC infusion rate of 15 and 0.6 mL/min/L total blood volume (TBV) resulted in premature discontinuation due to clotting. A ratio of 8 and AC infusion rate of 1.5-1.7 mL/min/L TBV with subsequent titration to higher levels were adopted for the second and third procedures. These changes resulted in greater acid-citrate-dextrose exposure, that was managed by continuous calcium chloride infusion. There was no hypocalcemia, hypotension, or distress during any procedure. A total of 15 × 106 CD34+ cells/kg were collected. This retrospective review illustrates that PBSC can be safely undertaken in children weighing less than 5 kg.

Peripartum Lipid Apheresis: Novel Management of Familial Hyperlipidemia in Pregnancy.

Familial hypercholesterolemia (FH) is a genetic lipid disorder associated with early-onset severe cardiovascular disease. Many FH therapeutics have not been studied in pregnancy, and management of patients with FH through pregnancy is limited. We present a patient with FH who was safely treated through pregnancy with combination therapy.

Head and Neck Reconstruction in Patients with Polycythemia Vera: Case Series and Literature Review.

Background Polycythemia vera (PV) is a myeloproliferative disease with overproduction of erythrocytes, leukocytes, and platelets causing an increased risk of both thrombosis and hemorrhage. There are limited reports and no established guidelines for managing such patients undergoing reconstructive surgery. Methods We present four patients with PV and head and neck cancer who required reconstruction after resection and provide a review of the current literature. Results Preoperatively, patients on cytoreductive therapy continued with their treatment throughout their hospital course and had hematologic parameters normalized with phlebotomy or transfusions if needed. Two patients who underwent free flap surgery (cases 1 and 2) had postoperative courses complicated by hematoma formation and persistent anemia, requiring multiple transfusions. Cases 3 and 4 (JAK2+ PV and JAK2- PV, respectively) underwent locoregional flap without postoperative complications. Conclusion Concomitant presentation of PV and head and neck cancer is uncommon and presents unique challenges for the reconstructive surgeon. Overall, we recommend that patients should have hematologic parameters optimized prior to surgery, continue ruxolitinib or hydroxyurea, and hold antiplatelet/anticoagulation per established department protocols. It is essential to engage a multidisciplinary team involving hematology, head and neck and reconstructive surgery, anesthesia, and critical care to develop a standardized approach for managing this unique subset of patients.

Performance Characteristics of DOAC-Remove for Neutralization of the Effects of Apixaban and Rivaroxaban in Lupus Anticoagulant Assays.

OBJECTIVES: This study established the performance characteristics of DOAC-Remove for neutralization of the effects of rivaroxaban and apixaban in lupus anticoagulant (LAC) testing. METHODS: Normal donor, LAC control, and patient samples were spiked with rivaroxaban or apixaban to simulate their effects on the dilute Russell's viper venom time (dRVVT), activated partial thromboplastin time (APTT), and dilute prothrombin time (dPT). Anti-Xa activity was measured after spiking and after DOAC-Remove neutralization. Accuracy, complex precision, and reference interval verification were evaluated. RESULTS: DOAC-Remove neutralized rivaroxaban and apixaban concentrations as high as 415 ng/mL and 333 ng/mL, respectively. Percentage positive and negative agreement between the baseline and postneutralization interpretations were 75% or higher for the dRVVT and APTT methods but not for the dPT method. Coefficients of variation (CVs) were 10% or less for all assays except the Staclot-LA delta, which had a standard deviation of 2.5 seconds or CV of 25% or less depending on the level. The laboratory's reference intervals were verified for the dRVVT and APTT assays after DOAC-Remove treatment but not for the dPT assays. CONCLUSIONS: DOAC-Remove appears to have acceptable performance characteristics for neutralizing the effects of rivaroxaban and apixaban in the dRVVT and APTT methods but not in the dPT method.

The Effects of Indirect- and Direct-Acting Anticoagulants on Lupus Anticoagulant Assays: A Large, Retrospective Study at a Coagulation Reference Laboratory.

OBJECTIVES: To investigate the effects of indirect- and direct-acting anticoagulants on the interpretation of lupus anticoagulant (LAC) assays. METHODS: A retrospective database review was performed to identify all LAC panels from November 2012 to November 2015. The positivity rates for three LAC tests were compared among various anticoagulant medications. RESULTS: This analysis included 7,721 LAC panels. Direct oral anticoagulants, warfarin, and unfractionated heparin (UFH) were associated with higher LAC positivity rates compared with patients not receiving documented anticoagulation (83% for argatroban, 58% for dabigatran, 72% for rivaroxaban, 53% for apixaban, 56% for warfarin, and 36% for UFH vs 29% for no anticoagulation, P < .025). Direct thrombin inhibitors mainly affected the activated partial thromboplastin time-based assays and the tissue thromboplastin inhibition index (TTI), while direct factor Xa inhibitors mainly affected the TTI and the dilute Russell viper venom ratio. CONCLUSIONS: Results of LAC testing performed while patients are receiving anticoagulant therapies should be interpreted with caution to avoid misdiagnosing patients with the antiphospholipid syndrome and potentially committing them to long-term anticoagulation therapy.

A Case of Unexplained Cerebral Sinus Thrombosis in a 22-Year-Old Obese Caucasian Woman.

Herein, we present the case of a 22-year old obese Caucasian woman female with no acquired thrombophilic risk factors who was diagnosed with extensive cerebral sinus thrombosis. A detailed thrombophilia workup demonstrated persistently elevated plasminogen activator inhibitor 1 (PAI-1) activity levels, with an elevated PAI-1 antigen concentration and homozygosity for the PAI-1 4G allele (4G/4G genotype). The patient was treated with indefinite warfarin anticoagulation medication due to the unprovoked nature of her thrombotic event. Disturbances in the fibrinolytic system, in particular PAI-1, have been related to an increased risk of arterial and venous thrombosis. In this article, we discuss the pathophysiology of hypofibrinolysis associated with elevated PAI-1 levels and the PAI-1 4G/5G polymorphism.