Arterial and Venous Thromboembolism in ALK-Rearrangement-Positive Non-small Cell Lung Cancer: A Population-Based Cohort Study.

INTRODUCTION: There is scarce data regarding the incidence of venous thromboembolism (VTE) and arterial thromboembolism (ATE) in the molecular subtypes of non-small cell lung cancer (NSCLC). We aimed to investigate the association between Anaplastic Lymphoma Kinase (ALK)-positive NSCLC and thromboembolic events. METHODS: A retrospective population-based cohort study of the Clalit Health Services database, included patients with NSCLC diagnosed between 2012 and 2019. Patients exposed to ALK-tyrosine-kinase inhibitors (TKIs) were defined as ALK-positive. The outcome was VTE (at any site) or ATE (stroke or myocardial infarction) 6 months prior to the diagnosis of cancer, until 5 years post-diagnosis. The cumulative incidence of VTE and ATE and hazard-ratios (HR) with 95% CIs were calculated (at 6- 12- 24 and 60-months), using death as a competing risk. Cox proportional hazards multivariate regression was performed, with the Fine and Gray correction for competing risks. RESULTS: The study included 4762 patients, of which 155 (3.2%) were ALK-positive. The overall 5-year VTE incidence was 15.7% (95% CI, 14.7-16.6%). ALK-positive patients had a higher VTE risk compared to ALK-negative patients (HR 1.87 [95% CI, 1.31-2.68]) and a 12-month VTE incidence of 17.7% (13.9-22.7%) compared to 9.9% (9.1-10.9%) in ALK-negative patients. The overall 5-year ATE incidence was 7.6% [6.8-8.6%]. ALK positivity was not associated with ATE incidence (HR 1.24 [0.62-2.47]). CONCLUSIONS: In this study, we observed a higher VTE risk, but not ATE risk, in patients with ALK-rearranged NSCLC relative to those without ALK rearrangement. Prospective studies are warranted to evaluate thromboprophylaxis in ALK-positive NSCLC.

Thrombogenicity and endothelial progenitor cells function during Acute myocardial infarction - comparison of Prasugrel versus Ticagrelor.

BACKGROUND: Thrombin generation (TG), platelet function and circulating endothelial progenitor cells (EPCs) have an important role in the pathophysiology of coronary artery disease (CAD). To date, the effect of novel P2Y12 inhibitors on these aspects has mostly been studied in the sub-acute phase following myocardial infarction. OBJECTIVES: Comparing the effects of prasugrel and ticagrelor on TG and EPCs in the acute phase of ST-segment elevation myocardial infarction (STEMI). METHODS: STEMI patients were randomized to either ticagrelor or prasugrel treatment. TG, platelet reactivity and EPCs were evaluated prior to P2Y12 inhibitor loading dose (T0), and one day following (T1). RESULTS: Between December 2018 - July 2021, 83 consecutive STEMI patients were randomized to ticagrelor (N = 42) or prasugrel (N = 41) treatment. No differences were observed at T0 for all measurements. P2Y12 reactivity units (PRU) at T1 did not differ as well (prasugrel 13.2 [5.5-20.8] vs. ticagrelor 15.8 [4.0-26.3], p = 0.40). At T1, prasugrel was a significantly more potent TG inhibitor, with longer lag time to TG initiation (7.7 ± 7.5 vs. 3.9 ± 2.1 min, p < 0.01), longer time to peak (14.1 ± 12.6 vs. 8.3 ± 9.7 min, p = 0.03) and a lower endogenous thrombin potential (AUC 2186.1 ± 1123.1 vs. 3362.5 ± 2108.5 nM, p < 0.01). Furthermore, EPCs measured by percentage of cells expressing CD34 (2.6 ± 4.1 vs. 1.1 ± 1.1, p = 0.01) and CD133 (2.3 ± 1.8 vs. 1.4 ± 1.5, p = 0.01) and number of colony forming units (CFU, 2.1 ± 1.5 vs. 1.1 ± 1.0, p < 0.01) were significantly higher in the prasugrel group. CONCLUSION: Among STEMI patients, prasugrel as compared to ticagrelor was associated with more potent TG inhibition and improved EPCs count and function.

Direct oral anticoagulants in patients with venous thromboembolism and hematological malignancies.

Data are needed on direct oral anticoagulants (DOACs) for the treatment of venous thromboembolism (VTE) in hematological malignancies (HM). Retrospective studies to date lacked a control group and did not focus on patients with VTE. Out aim was to assess the incidence of VTE recurrence and bleeding in HM patients treated with low molecular weight heparin (LMWH) or DOACs for acute VTE. This is a retrospective cohort study including patients with active HM and newly-diagnosed VTE, indexed on the first day of anticoagulation and followed for 12 months. The outcome was a composite of recurrent VTE, major bleeding or clinically relevant non-major bleeding. Cumulative incidence [95% confidence interval (CI)] was calculated for each anticoagulation group (LMWH, DOAC) and hazard ratios (HR) were calculated using cox-proportional hazards model, with death as a competing risk. 143 HM patients treated with LMWH (96) or DOACs (47) for acute VTE were included. The most common HM types were lymphoma in 83 (58%) and plasma cell dyscrasia in 32 (22.3%). The 12-month cumulative incidence of the composite outcome was 24.2% (95% CI 15.9-33.5%; n = 22) in the LMWH group and 18.5% (8.5-31.5%; n = 8) in the DOAC group (HR 1.51 [0.695-3.297]). Two recurrent VTE occurred (both in the DOAC group while off-treatment). Nine (9.4%) LMWH-treated patients had major bleeding compared to 1 (2.1%) DOAC-treated patient (HR 4.85 [0.64-36.56]). This study generates the hypothesis that DOACs may be a safe and effective alternative to LMWH for VTE in patients with HM types represented in the study.

Exacerbation of immune thrombocytopenia following initial and booster vaccination with Pfizer-BioNTech COVID-19 vaccine.

As the immune thrombocytopenia exacerbation rate after booster COVID-19 vaccines is unknown, we explore the rates after first, second and booster Pfizer-BioNTech COVID-19 vaccines. A retrospective study of adult ITP patients, receiving 1-3 vaccines was performed. The primary outcome was clinical ITP exacerbation defined as platelet count decrease requiring initiation/escalation of ITP treatment and/or new medical attention due to bleeding, within 3 months. Secondary outcome was any clinically relevant platelet decrease during the 3 months post-vaccination. The study included 93 ITP patients receiving 1 (n = 2), 2 (n = 22) or 3 (n = 69) vaccines. ITP exacerbation occurred in 2/93 (2.2%) patients following initial vaccination and in 3/69 (4.3%) following booster dose. Clinically relevant platelet decreases after initial doses occurred in 8/72 (11.1%) patients and in 8/39 (20.5%) after the booster. Clinical ITP exacerbation after booster doses did not follow clinical exacerbation after initial doses. Half of patients with clinically relevant platelet decreases after booster dose also had clinically relevant decreases following initial vaccination. We concluded that clinical ITP exacerbation is infrequent following Pfizer-BioNTech COVID-19 vaccine. Clinical exacerbation after booster doses was not preceded by clinical exacerbation after initial doses. Clinically relevant platelet decreases after booster doses occur frequently in patients with clinically relevant decreases after initial doses.

Apixaban Level and Its Influence on Immunosuppression and Graft Outcome in Kidney Transplant Recipients With Atrial Fibrillation.

BACKGROUND: Currently, there is limited information on the level of apixaban in kidney transplant (KT) patients with atrial fibrillation and the influence of apixaban therapy on the level of immunosuppression and graft function. METHODS: This was a cross-sectional prospective study of 19 KT patients treated with apixaban. The levels of apixaban were measured using a chromogenic assay calibrated for apixaban and compared with those predicted by the manufacturer. Mean immunosuppression trough levels before and after apixaban treatment initiation were calculated using 3 consecutive measurements. Apixaban levels were compared with a historical control group comprising of 20 nontransplant patients with atrial fibrillation who were treated with the standard 5-mg bid apixaban dosage. RESULTS: All KT patients should have been treated with the standard 5-mg bid apixaban dosage according to the clinical parameters; however, 7 were inappropriately treated with a reduced dosage (2.5-mg bid). There was no significant difference in apixaban level between KT patients treated with the 5-mg bid dosage and nontransplant patients. No KT patient administered the standard dose had out-of-range levels. Peak GM level was significantly lower in KT patients administered an inappropriately reduced dose (P = 0.05). Two patients had below-range peak levels. Apixaban treatment initiation had minimal influence on the level of immunosuppression. Furthermore, it had no adverse impact on graft function. CONCLUSIONS: Similar to nontransplant patients, KT patients administered the standard 5-mg bid dosage had apixaban levels that were well within the recommended manufacturers' expected ranges. In addition, this dosage had minimal influence on immunosuppression and no effect on graft function.

An Early Unexpected Immune Thrombotic Thrombocytopenic Purpura Relapse Associated with SARS-CoV-2 Infection: A Case Report and Literature Review.

SARS-CoV-2 has been reported as a possible triggering factor for the development of several autoimmune diseases and inflammatory dysregulation. Here, we present a case report of a woman with a history of systemic lupus erythematosus and antiphospholipid syndrome, presenting with concurrent COVID-19 infection and immune thrombotic thrombocytopenic purpura (TTP). The patient was treated with plasma exchange, steroids, and caplacizumab with initial good response to therapy. The course of both TTP and COVID-19 disease was mild. However, after ADAMTS-13 activity was normalized, the patient experienced an early unexpected TTP relapse manifested by intravascular hemolysis with stable platelet counts requiring further treatment. Only 3 cases of COVID-19 associated TTP were reported in the literature thus far. We summarize the literature and suggest that COVID-19 could act as a trigger for TTP, with good outcomes if recognized and treated early.

Thrombin Generation in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

BACKGROUND: The optimal antithrombotic treatment for patients with atrial fibrillation (AF) that undergo percutaneous coronary intervention (PCI) is controversial. Dual therapy (clopidogrel and a direct oral anticoagulant [DOAC]) is safer than triple therapy (warfarin, aspirin, and clopidogrel), while efficacy is unclear. We aimed to evaluate thrombin generation (TG) under dual and triple therapy. METHODS: A noninterventional prospective trial in patients with AF undergoing PCI. Patients received 4 weeks of triple therapy with aspirin, clopidogrel, and a DOAC followed by aspirin withdrawal. TG was measured in platelet-rich plasma (PRP) and platelet-poor plasma (PPP) at 3 five to 21 points, day 1 after PCI (TIME 0), 4 weeks after PCI (TIME 1), and 2 weeks after aspirin withdrawal (TIME 2). RESULTS: Twenty-three patients (18 men, median age 78 years, 83% with acute coronary syndrome) were included. Endogenous thrombin potential (ETP) in PPP was high at TIME 0 compared with TIME 1 (ETP 3,178 ± 248 nM vs. 2,378 ± 222 nM, p = 0.005). These results remained consistent when measured in PRP. No significant difference in ETP was found before (TIME 1) and after aspirin withdrawal (TIME 2) although few patients had high ETP levels after stopping aspirin. CONCLUSIONS: TG potential is high immediately after PCI and decreases 4 weeks after PCI in patients receiving triple therapy. TG remains constant after aspirin withdrawal in most patients, suggesting that after 1 month the antithrombotic effect of dual therapy may be similar to triple therapy.

Pregnancy and non-pregnancy related immune thrombotic thrombocytopenic purpura in women of reproductive age.

Pregnancy is a precipitating factor for immune thrombotic thrombocytopenic purpura (iTTP). We compared the clinical course and outcomes of iTTP in women of reproductive age, between those with pregnancy- and non-pregnancy-related iTTP. A review of all reproductive-aged women diagnosed with iTTP during 2010-2019 in seven university hospitals in Israel. Of 42 cases of iTTP, 12 (28.6%) were pregnancy-related. At presentation, the laboratory profiles did not differ significantly between those with pregnancy- and non-pregnancy-related iTTP, including hemoglobin (median 8.4 vs 8.0 g/dL), platelet count (12.5 vs. 11.5 X 109/L); and levels of bilirubin (1.23 vs. 1.82 mg/dL), lactate dehydrogenase (1615 vs. 1701 U/L), creatinine (0.61 vs. 0.79 mg/dL) and anti-ADAMTS13 antibodies titer (75 vs. 82 U/mL). The proportions of women with renal, neurologic, or hepatic involvement were similar between the groups. Cardiac involvement was more common among those with pregnancy-related disease (25.0% vs. 3.3%, P = 0.06). The median number of courses of plasma-exchange therapy was 11 for both groups. All the women were treated with parenteral corticosteroids and the rate of adjunctive treatments did not differ between the groups (P = 0.30). Four women (one-third) with pregnancy-related disease had preeclampsia. Two women (16.7%) with pregnancy-related iTTP died during the acute episode (P = 0.07); no deaths were observed in the non-pregnancy-related group. Among reproductive-aged women with iTTP, most clinical and laboratory profiles were similar between those with pregnancy- and non-pregnancy-related disease. However, the higher rates of cardiac involvement and mortality among women with pregnancy-related iTTP highlight its challenging management.

Anticoagulation in patients with atrial fibrillation, thrombocytopenia and hematological malignancy.

Managing anticoagulation in hematological malignancy patients with atrial fibrillation and thrombocytopenia is a clinical challenge with limited data. We aimed to identify anticoagulation management strategies and evaluate bleeding and thrombosis rates associated with each approach. A retrospective cohort study in Israel and the Netherlands was conducted. Patients with hematological malignancy and atrial fibrillation were indexed when platelets were < 50 × 109/L and followed for 30 days. The cohort included 61 patients of whom 42 (69%) had anticoagulation held at index. On multivariate analysis, holding anticoagulation was associated with age < 65 years and atrial fibrillation diagnosed within 30 days prior index. Clinically relevant bleeding was diagnosed in 7 (16.7%) and 1 (5.3%) of patients who had anticoagulation held and continued respectively, while arterial thromboembolism occurred in 1 patient in each group (2.4% and 5.3%, respectively). All-cause mortality rate was high at 45%. Accordingly, the 30-day bleeding risk may outweigh the risk of arterial thromboembolism in hematological malignancy, platelets < 50 × 109/L and atrial fibrillation.

Epidural/spinal anesthesia during delivery in women with factor XI deficiency, a single center experience.

INTRODUCTION: The safety of neuro-axial anaesthesia (epidural/spinal) at labour of women with partial factor XI (FXI) deficiency is uncertain. Although FXI deficiency is frequent in Ashkenazi Jews, it is not routinely measured before labour. Our institute serves a large Ashkenazi population. We assumed that 10% of them have undiagnosed FXI deficiency. AIM: Assess the incidence, bleeding tendency and coagulation status among Jewish Ashkenazi women with FXI deficiency that underwent neuro-axial anaesthesia at delivery. METHODS: Jewish Ashkenazi women who underwent neuro-axial anaesthesia at labour completed the SSC ISTH bleeding assessment tool (BAT) and had blood drawn for coagulation tests, FXI and thrombin generation after labour. Estimation for 10 years was calculated from the 1-year sample. RESULTS: We recruited 261 women during 12 months. Among them, 39 (15%) had FXI deficiency (<70%) with median FXI levels of 63% (range: 33%-70%). Around 50% of them underwent amniocentesis in the current pregnancy and prior neuro-axial anaesthesia with no bleeding complications. BAT score and thrombin generation did not differ between women regardless of FXI status. aPTT was longer in women with partial FXI deficiency (median - 28.6 sec vs 26.3 sec, P < .001, Table 2), although within the normal range in all women. No bleeding complications after neuro-axial anaesthesia at delivery were reported in our centre in the last decade though, and according to our estimation, at least 2150 women had partial FXI deficiency. CONCLUSIONS: A significant number of Jewish Ashkenazi women with undiagnosed partial FXI deficiency undergo neuro-axial anaesthesia at labour without bleeding complications.

Venous Thromboembolism Complicated with COVID-19: What Do We Know So Far?

Coronavirus disease (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is responsible for the ongoing 2019-2020 pandemic. Venous thromboembolism (VTE), a frequent cardiovascular and/or respiratory complication among hospitalized patients, is one of the known sequelae of the illness. Hospitalized COVID-19 patients are often elderly, immobile, and show signs of coagulopathy. Therefore, it is reasonable to assume a high incidence of VTE among these patients. Presently, the incidence of VTE is estimated at around 25% of patients hospitalized in the intensive care unit for COVID-19 even under anticoagulant treatment at prophylactic doses. In this review, we discuss present knowledge of the topic, the unique challenges of diagnosis and treatment of VTE, as well as some of the potential mechanisms of increased risk for VTE during the illness. Understanding the true impact of VTE on patients with COVID-19 will potentially improve our ability to reach a timely diagnosis and initiate proper treatment, mitigating the risk for this susceptible population during a complicated disease.

Prothrombin Complex Concentrate before Urgent Surgery in Patients Treated with Rivaroxaban and Apixaban.

INTRODUCTION: Patients treated with direct Xa inhibitors may require urgent surgery. Administration of prothrombin complex concentrate (PCC) in this setting is common; however, it is based on limited experience in healthy volunteers. OBJECTIVE: To characterize the population receiving PCC for apixaban/rivaroxaban reversal prior to an urgent surgery and evaluate its efficacy and safety. METHODS: This was a retrospective study in 2 tertiary hospitals. Bleeding was evaluated based on surgical reports, hemoglobin drop, and the use of blood products or additional PCC during 48 h. Safety measures were thrombotic complications and 30-day mortality. RESULTS: Sixty-two patients aged 80.7 ± 9 years, treated with apixaban (39.63%) or rivaroxaban (23.37%), received PCC before an urgent surgery/procedure. Most underwent abdominal operation (61%), orthopedic surgery (13%), or transhepatic cholecystostomy insertion (10%). Bleeding during surgery was reported in 3 patients (5%), no patient required additional PCC, and 16 patients (26%) received packed cells (median: 1 unit, range: 1-5). The 30-day mortality and thrombosis rates were 21% (n = 13) and 3% (n = 2), respectively. The cause of death was related to the primary disease, most commonly sepsis. No patient died due to bleeding/thrombosis. CONCLUSIONS: Our results support the use of PCC to achieve hemostasis in patients treated with Xa inhibitors prior to an urgent surgery.

Factors associated with pregnancy outcomes in women with a history of cerebral sinus venous thrombosis.

To collect and summarize pregnancy outcomes among women with a history of cerebral sinus vein thrombosis (CSVT). A retrospective multicenter case-control study. The study group comprised all women diagnosed with CSVT during 2004-2018 at four university hospitals, and with follow-up data of pregnancy. A control group of women with a singleton pregnancy was established by matching, four-to-one, according to maternal age. The data of 74 pregnancies of 65 women with CSVT were analyzed. The median time-to-pregnancy interval from the CSVT was 4.2 [2.7-6.8] years. Anticoagulation therapy in the form of enoxaparin was administered in 68 (91.9%) pregnancies. Adjunctive low-dose aspirin was used throughout 12 (16.2%) pregnancies. Overall, 54 (73.0%) of the pregnancies ended in live births and 20 (27.0%) in miscarriage. The use of anticoagulation therapy during pregnancy was positively associated with live birth outcome (P < 0.001). Late adverse outcomes were encountered in 19 (25.7%) pregnancies, including the delivery of a small for gestational age infant (n = 12), gestational hypertensive disorders (n = 6) and placental abruption (n = 3). The use of adjunctive aspirin was associated with a lower rate of late adverse pregnancy outcomes (P = 0.03). No recurrent CSVT, thrombosis at other sites, and major bleeding episodes were observed during pregnancy. Live-birth rate was higher (P = 0.007) and the rate of late adverse outcome was lower (P = 0.01) for the control (n = 296) than the study group. Among pregnant women with a prior CSVT, no recurrent thrombosis events were observed during gestation. The use of prophylactic anticoagulation was associated with live birth. The use of adjunctive aspirin should be further studied in this setting, as its utilization correlated with a lower rate of late pregnancy complications.

Thrombosis, anticoagulation and outcomes in malignant superior vena cava syndrome.

Anticoagulation is often used in superior vena cava syndrome (SVCS) associated with cancer (i.e malignant SVCS), even without thrombosis, but its effect on outcomes has not been reported. We aimed to determine factors and outcomes associated with thrombosis and anticoagulation in malignant SVCS. Patients with malignant SVCS diagnosed on computerized tomography (CT) were retrospectively included, indexed at diagnosis and followed for 6 months using medical records. The cohort included 183 patients with malignant SVCS of which 153 (84%) were symptomatic. Thirty of the 127 patients (24%) with a reviewable baseline CT had thrombosis of the SVC or tributaries at diagnosis. Patients with baseline thrombosis more often had symptomatic SVCS (p < 0.01). 70% (21/30) of patients with thrombosis and 52% (49/97) of those without thrombosis at baseline received anticoagulation, most often at therapeutic doses. Thrombosis occurred in 5/39 patients with anticoagulation (13%) compared to 2/18 (11%) of those without, during follow-up (p = 0.85). Anticoagulation was associated with a reduction in risk of SVC stent placement during follow-up that did not reach statistical significance (HR 0.47, 95% CI 0.2-1.13, p = 0.09). Major bleeding occurred in 7 (4%) patients, six of whom received anticoagulation (four therapeutic and two intermediate dose). Neither thrombosis nor anticoagulation affected survival. Anticoagulation is commonly used as primary prevention but its benefit remains to be proven. The role of reduced-dose anticoagulation in non-thrombotic malignant SVCS should be prospectively assessed.

Meal intake increases circulating procoagulant microparticles in patients with type 1 and type 2 diabetes mellitus.

Diabetes mellitus (DM) is associated with prothrombotic alterations, and postprandial hyperglycemia is an independent risk factor for cardiovascular complications. We therefore investigated whether a standardized mixed meal alters circulating microparticles (MPs) and their procoagulant activity in DM patients. Patients with DM type 1 (T1DM, n = 11) and type 2 (T2DM; n = 9) were studied before and 90 min after a standardized meal (without premeal insulin). MPs in plasma derived from platelets (PMPs), endothelial cells (EMPs), or monocytes (MMPs) were measured by flow cytometry. MP-induced thrombin generation in plasma was assessed by a calibrated automated thrombogram. In the fasting state, MPs did not differ significantly between T1DM and T2DM. Meal intake increased the following microparticles: PMPs expressing phosphatidylserine (by 55%, on average), P-selectin (by 86%), and tissue factor (TF; by 112%); EMPs expressing E-selectin (by 96%) and MMPs expressing TF (by 164%), with no significant group differences between T1DM and T2DM. There were no increments in EMPs expressing phosphatidylserine or TF. Meal intake increased MP-induced thrombin generation similarly in T1DM and T2DM with increased endogenous thrombin potential (p = 0.02) and peak thrombin (p = 0.03) and shortened time to peak (p = 0.02). Phosphatidylserine inhibition by lactadherin completely abolished MP-induced thrombin generation, while an anti-TF antibody had no effect. In conclusion, meal intake increased several types of circulating MPs in patients with diabetes mellitus. These MPs have a procoagulant potential, which is related to phosphatidylserine expression and negatively charged MP surfaces rather than to TF.

Computed Tomography Findings Associated With 30-Day Mortality in Patients With Malignant Superior Vena Cava Syndrome.

OBJECTIVE: The objective of this study was to identify radiological and clinical factors associated with early mortality in malignant superior vena cava syndrome (SVCS). MATERIALS AND METHODS: Chest computed tomography studies of 127 patients with malignancy-associated SVCS were retrospectively reviewed. Involvement of SVC and tributaries, pleural and pericardial effusions, pulmonary artery involvement, and ancillary findings were documented. Univariate and multivariate models determined associations between radiological and clinical variables, and 30-day mortality. RESULTS: Thirty-day mortality rate was 16.5% (n = 21). Factors associated with 30-day mortality on univariate analysis included age, cancer stage, SVCS clinical severity, left jugular vein obstruction, number of involved veins, pulmonary arteries involvement, and presence of pleural effusions. Age, SVCS clinical severity, number of veins involved, and pleural effusions were positively associated with 30-day mortality on multivariate analysis. CONCLUSIONS: Selected clinical and radiological variables are associated with early death in malignant SVCS. These factors may identify a subgroup of patients who may benefit from treatment escalation.

[THROMBOCYTOPENIA, LEG EDEMA AND SHORTNESS OF BREATH FOLLOWING CORONARY ARTERY BYPASS SURGERY].

INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is the most important non-hemorrhagic complication of heparin treatment. We report a case of a major thromboembolic event accompanied by thrombocytopenia following heparin exposure during coronary artery bypass graft surgery. Thrombocytopenia was documented one month after the surgery, and a major thromboembolic event which led to the patient's death diagnosed 6 weeks after heparin exposure. We discuss the pathophysiology and clinical aspects of heparin-induced thrombocytopenia, focusing on the unique features of this patient, including late persistent thrombocytopenia.

Intravenous immunoglobulin-induced acute thrombocytopenia.

BACKGROUND: Intravenous immunoglobulin (IVIG) has known efficacy in various hematologic conditions, including immune thrombocytopenic purpura. STUDY DESIGN AND METHODS: We present the clinical course of a patient with splenic marginal zone lymphoma, who developed acute thrombocytopenia on three consecutive episodes, with nadir counts of 27 × 109 , 50 × 109 , and 9 × 109 /L, upon administration of Intratect IVIG for hypogammaglobulinemia. An immunofluorescence test applying flow cytometry and monoclonal antibody immobilization of platelet antigens (MAIPA) assay were used to evaluate the reaction between IgG present in the IVIG preparations and the patient's or healthy donors' platelets (PLTs). RESULTS: A strong direct binding reaction was observed between the patient's PLTs and Intratect IgG using both methods. A similar reaction failed to materialize with controls. Binding was not antigen specific according to MAIPA. CONCLUSIONS: This is the first reported case of thrombocytopenia as a possible adverse effect of IVIG.

Assessment of procoagulant potential in patients with reactive thrombocytosis and its association with platelet count.

OBJECTIVE: We aimed to determine hemostatic changes and characterize the procoagulant potential among patients with reactive thrombocytosis (RT). METHODS: Sixty patients with RT (median platelet count 718 × 109 /L) and 20 healthy persons were tested for complete blood count, C-reactive protein, von Willebrand factor (VWF), factor VIII and fibrinogen, and thrombin generation. Platelet studies, including light transmission aggregometry and Cone and Plate(let) Analyzer, were also conducted. Reticulated platelets and platelet P-selectin expression were measured using flow cytometry. RESULTS: Compared to patients with mild thrombocytosis (platelet count 500-700 × 109 /L; n = 27), those with moderate-to-severe thrombocytosis (platelet count >700 × 109 /L; n = 33) had significantly higher fibrinogen, factor VIII, and VWF antigen and activity levels; higher endogenous thrombin potential, peak thrombin generation and velocity index levels, and shorter time-to-peak thrombin level. VWF antigen and activity, fibrinogen, and factor VIII were positively associated with platelet count, whereas VWF activity/antigen ratio was inversely correlated. In a multivariate analysis of RT and control participants, only platelet count predicted endogenous thrombin potential with a positive-linear correlation. No patients developed acquired von Willebrand syndrome. CONCLUSIONS: As determined by thrombin generation, RT was associated with in vitro prothrombotic tendency, which correlated with platelet count. This may explain the increased thromboembolic risk previously reported in patients with RT.

Thromboembolic Events Following Splenectomy: Risk Factors, Prevention, Management and Outcomes.

BACKGROUND: Thromboembolic events following splenectomy are not uncommon. However, the role of thromboprophylaxis and risk factors for thrombosis, as well as the clinical course and outcomes, are not well characterized. METHODS: A retrospective review of individuals who underwent splenectomy between January 2006 and December 2015 in two university hospitals. RESULTS: Overall, 297 patients underwent splenectomy [open splenectomy (n = 199), laparoscopic splenectomy (n = 98)]. Mechanical (thigh-length pneumatic compression stockings) and pharmacologic thromboprophylaxis (40 mg enoxaparin daily, starting 12 h after surgery until discharge) was provided for all patients. One hundred and sixteen patients (39%) also received an extended thromboprophylaxis course of enoxaparin for 2-4 weeks after discharge. Twenty-three patients (7.7%) experienced thrombotic complications following splenectomy, including 16 cases (5.4%) of portal-splenic mesenteric venous thrombosis (PSMVT), 5 (1.7%) pulmonary embolism and 2 (0.7%) deep vein thrombosis. Longer operative time (mean operative time of 405 vs. 273 min, P = 0.03) was independently associated with PSMVT. Post-splenectomy thrombocytosis was not associated with thrombosis (P = 0.41). The overall thrombosis rate was significantly lower in patients who received an extended thromboprophylaxis course following splenectomy (3.4 vs. 10.5%, P = 0.02). Complete resolution of thrombosis was observed in most cases (n = 20, 87.0%), with no recurrent thrombosis during a mean follow-up of 38 ± 25 months. CONCLUSIONS: Thromboembolic complications, mainly PSMVT, are common following splenectomy. Longer operative time was associated with thrombosis. Significantly lower rates of thrombosis were found in patients who received an extended thromboprophylaxis course.