Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder mediated by platelet-activating antibodies that target complexes of platelet factor 4 (PF4) and heparin. Because nearly all patients undergoing cardiopulmonary bypass (CPB) are exposed to heparin and experience a postoperative platelet count fall, it is not surprising that HIT is commonly suspected in this population. However, the incidence of HIT in cardiac surgery patients who receive intraoperative and postoperative unfractionated heparin is much lower than the incidence of suspected HIT, being approximately 1 to 2%. Clinical diagnosis may therefore be particularly challenging because of the need to distinguish the common platelet count fall associated with CPB and surgery from the much less common platelet count fall associated with HIT. A biphasic platelet count pattern is characteristic of HIT in this setting. Laboratory diagnosis is also difficult because of the high frequency of anti-PF4/heparin antibody seropositivity after cardiac surgery in patients without HIT. A unique aspect of management in the cardiac surgery setting is selecting an anticoagulant for intraoperative use in patients with a history of HIT who require cardiac surgery. In this article, we review the epidemiology, clinical diagnosis, and laboratory diagnosis of HIT in cardiac surgery patients and present a conceptual framework for selecting intraoperative anticoagulation in patients with a history of HIT.

In acquired hemophilia A (AHA), autoantibodies to coagulation factor VIII (FVIII) neutralize FVIII activity leading to a potentially severe bleeding diathesis that carries a high rate of morbidity and mortality. This disorder is rare and occurs mainly in adults over 60 years of age or in the postpartum period. The diagnosis should be suspected in patients with new-onset bleeding without a personal or family history of bleeding and can be confirmed via specific assays for FVIII inhibitors. Treatment involves both hemostatic therapies to decrease bleeding and immune modulation strategies to re-establish immune tolerance to FVIII. There are limited data on treatment for refractory disease, based mostly on small case series. Registry studies have informed consensus guidelines for optimal hemostatic therapies and initial immunosuppressive therapies. Additional studies are needed to evaluate novel hemostatic agents and develop biomarkers to risk-stratify treatment while limiting adverse events.

Background The presence of a hypercoagulable disorder such as heparin‐induced thrombocytopenia (HIT) may protect against anticoagulant‐associated bleeding. Objectives To determine the incidence of major bleeding in patients with suspected HIT. Methods We performed a retrospective analysis of 310 patients suspected of having HIT from the Hospital of the University of Pennsylvania and an affiliated community hospital. We compared the cumulative incidence of major bleeding following suspicion for HIT by ultimate HIT status (HIT+ or HIT−) and exposure to an alternative anticoagulant (Tx+ or Tx−). Secondary outcomes included the incidence of new/progressive thrombosis and 30‐day mortality. Results The incidence of major bleeding was high in the HIT+Tx+, HIT− Tx+, and HIT−Tx− groups (35.7%, 44.0%, and 37.3%, respectively). The time to first major bleeding event did not differ between groups (P = .24). Factors associated with increased risk of major bleeding included intensive care unit admission (HR 2.24, 95% CI 1.44‐3.47), platelet count < 25 × 109/L (HR 2.13, 1.10‐4.12), and renal dysfunction (HR 1.56, 1.06‐2.27); 35.7% of HIT+Tx+, 13.8% HIT−Tx+, and 9.3% of HIT−Tx− patients experienced new or progressive thrombosis. Mortality was similar among the three groups (26.2% HIT+Tx+, 34.5% HIT−Tx+, and 26.7% of HIT−Tx− [P = .34]). Conclusions Among patients with suspected HIT, major bleeding was common regardless of HIT status. Contrary to our hypothesis, HIT+ patients were not protected from major bleeding. A better understanding of bleeding risk is needed to inform management decisions in patients with suspected HIT.

Objectives CD8T cells lacking CD28 were originally reported by Wedderburn and colleagues as a characteristic feature of JIA, but the relevance of these unusual cells to JIA remains to be elucidated. Because of recent evidence that CD28 loss is typical of terminally differentiated lymphocytes, we examined for functional subsets of CD8T cells in JIA. Methods Following informed consent/assent, blood and/or waste synovial fluid were collected from children with definite diagnosis of JIA (n = 98). De-identified blood (n = 33) and cord blood (n = 13) samples from healthy donors were also collected. CD8T and CD4T cells were screened for novel receptors, and where indicated, bioassays were performed to determine functional relevance of the identified receptor. Results Patients had a naïve T cell compartment with shortened telomeres, and their entire T cell pool had reduced proliferative capacity. They had an over abundance of CD31+CD28null CD8T cells, which was a significant feature of oligoarticular JIA (n = 62) compared to polyarticular JIA (n = 36). CD31+CD28null CD8T cells had limited mitotic capacity, and expressed high levels of the senescence antigens γH2Ax and/or p16. Ligation of CD31, independent of the TCR, sufficiently induced tyrosine phosphorylation, vesicle exocytosis, and production of IFN-γ and IL-10. Conclusion These data provide the first evidence for cell senescence, represented by CD31+CD28null CD8T cells, in the pathophysiology of JIA. Activation of these unusual cells in a TCR-independent manner suggests they are maladaptive, and could be potential targets for immunotherapy.