Real world management of individuals with severe FXI deficiency and its impact on clinical outcomes: Experience from a haemophilia treatment centre.

INTRODUCTION: The management of Factor XI deficiency is challenged by a variable association between FXI level and bleeding phenotype. Additionally, there is scarce data describing management strategies and their outcomes, specifically bleeding, thrombosis, and other complications. AIMS: To evaluate bleeding, thrombosis, and other complications in individuals with severe FXI deficiency seen in our comprehensive haemophilia treatment centre (HTC). Peri-procedural management strategies and the resulting impact on bleeding and other clinically relevant outcomes were reported. METHODS: Retrospective review of the electronic medical record of adult patients with severe FXI deficiency (< 20% activity) seen at a New York City comprehensive HTC between 2017 and 2022. Procedures, haemostatic management, and outcomes were collected and analysed. RESULTS: We identified 38 individuals (64%) females with severe FXI deficiency. The mean age was 56 ± 21 years (SD). The median FXI activity level was 3% (IQR: 1-8%). The mean BAT score was 3.1 ± 2.4; (52%) individuals did not have a history of bleeding. A total of 256 surgeries and procedures were performed. There was reduced bleeding with preventative or reactive treatment during procedures. Arterial but not venous thrombotic complications were observed. Plasma was mostly used for procedures associated with higher risk of bleeding and antifibrinolytics for procedures at sites of high fibrinolysis. CONCLUSIONS: Current management strategies pose a burden of care for these patients and manifested as nonbleeding adverse events and changes in clinical management. These findings highlight the need for novel investigation in predicting and managing bleeding for individuals with severe FXI deficiency.

Intermediate-dose versus low-dose low-molecular-weight heparin in pregnant and post-partum women with a history of venous thromboembolism (Highlow study): an open-label, multicentre, randomised, controlled trial.

BACKGROUND: Pregnancy-related venous thromboembolism is a leading cause of maternal morbidity and mortality, and thromboprophylaxis is indicated in pregnant and post-partum women with a history of venous thromboembolism. The optimal dose of low-molecular-weight heparin to prevent recurrent venous thromboembolism in pregnancy and the post-partum period is uncertain. METHODS: In this open-label, randomised, controlled trial (Highlow), pregnant women with a history of venous thromboembolism were recruited from 70 hospitals in nine countries (the Netherlands, France, Ireland, Belgium, Norway, Denmark, Canada, the USA, and Russia). Women were eligible if they were aged 18 years or older with a history of objectively confirmed venous thromboembolism, and with a gestational age of 14 weeks or less. Eligible women were randomly assigned (1:1), before 14 weeks of gestational age, using a web-based system and permuted block randomisation (block size of six), stratified by centre, to either weight-adjusted intermediate-dose or fixed low-dose low-molecular-weight heparin subcutaneously once daily until 6 weeks post partum. The primary efficacy outcome was objectively confirmed venous thromboembolism (ie, deep-vein thrombosis, pulmonary embolism, or unusual site venous thrombosis), as determined by an independent central adjudication committee, in the intention-to-treat (ITT) population (ie, all women randomly assigned to treatment). The primary safety outcome was major bleeding which included antepartum, early post-partum (within 24 h after delivery), and late post-partum major bleeding (24 h or longer after delivery until 6 weeks post partum), assessed in all women who received at least one dose of assigned treatment and had a known end of treatment date. This study is registered with ClinicalTrials.gov, NCT01828697, and is now complete. FINDINGS: Between April 24, 2013, and Oct 31, 2020, 1339 pregnant women were screened for eligibility, of whom 1110 were randomly assigned to weight-adjusted intermediate-dose (n=555) or fixed low-dose (n=555) low-molecular-weight heparin (ITT population). Venous thromboembolism occurred in 11 (2%) of 555 women in the weight-adjusted intermediate-dose group and in 16 (3%) of 555 in the fixed low-dose group (relative risk [RR] 0·69 [95% CI 0·32-1·47]; p=0·33). Venous thromboembolism occurred antepartum in five (1%) women in the intermediate-dose group and in five (1%) women in the low-dose group, and post partum in six (1%) women and 11 (2%) women. On-treatment major bleeding in the safety population (N=1045) occurred in 23 (4%) of 520 women in the intermediate-dose group and in 20 (4%) of 525 in the low-dose group (RR 1·16 [95% CI 0·65-2·09]). INTERPRETATION: In women with a history of venous thromboembolism, weight-adjusted intermediate-dose low-molecular-weight heparin during the combined antepartum and post-partum periods was not associated with a lower risk of recurrence than fixed low-dose low-molecular-weight heparin. These results indicate that low-dose low-molecular-weight heparin for thromboprophylaxis during pregnancy is the appropriate dose for the prevention of pregnancy-related recurrent venous thromboembolism. FUNDING: French Ministry of Health, Health Research Board Ireland, GSK/Aspen, and Pfizer.

Reduced expression of annexin A2 is associated with impaired cell surface fibrinolysis and venous thromboembolism.

Reduced plasma fibrinolysis has been identified as a potential risk factor for venous thromboembolism (VTE), but the role of cell surface fibrinolysis in VTE is unknown. The annexin A2/S100A10 complex serves as a coreceptor for plasminogen and tissue plasminogen activator (tPA), augmenting plasmin generation by 60-fold on the endothelial cell surface. Several studies in both mice and humans support the concept that A2 regulates fibrin homeostasis and intravascular thrombosis in vivo. Here, we examined A2 protein expression and function in 115 adult subjects with VTE and 87 healthy controls. Using peripheral blood mononuclear cells as a surrogate for endothelial cells, we found a 41% mean decrease in cell surface tPA-dependent fibrinolytic activity in subjects who had a positive personal and family history of VTE but tested negative for known inherited thrombophilias (ITs). A2 protein was reduced on average by 70% and messenger RNA levels by 30%, but neither decrease correlated with anticoagulant therapy. Neither cell A2 protein nor cell surface plasmin generation correlated with plasma-based clot lysis times, suggesting that the plasma and cell surface fibrinolytic systems operate independently of one another. These data suggest that reduced expression of annexin A2 protein is associated with cell surface hypofibrinolysis and may represent a novel risk factor for IT.

Management and outcomes of women with antiphospholipid syndrome during pregnancy.

Women with antiphospholipid syndrome (APS) have an increased risk of adverse pregnancy outcomes. To define clinical, serologic, and treatment factors that can predict outcomes in pregnant women with APS. Retrospective cohort study of pregnant women with APS evaluated at a university medical center between January 2006 and August 2021. Demographics, personal and family history of thrombosis, autoimmune disease, antithrombotic use, pregnancy outcomes, maternal and fetal complications were collected. We compared pregnancy outcomes in the presence or absence of lupus anticoagulant (LA), systemic lupus erythematosus (SLE), prior thrombosis or pregnancy losses, and antithrombotic use. There were 169 pregnancies in 50 women; 79 (46.7%) occurred after maternal diagnosis of APS. The most common antithrombotic regimen was aspirin and low molecular weight heparin (LMWH) in 26.6% of pregnancies; 55.0% of all pregnancies and 68.4% of pregnancies post-APS diagnosis resulted in a live birth. In age-adjusted analyses, aspirin plus LMWH regardless of dosage was associated with significantly higher odds of live birth compared with no antithrombotic use (OR = 7.5, p < 0.001) and compared with aspirin alone (OR = 13.2, p = 0.026). SLE increased the risk for preterm birth and preeclampsia. A positive LA did not impact the outcomes evaluated and anticardiolipin IgM decreased the risk of pre-eclampsia. The presence of SLE is a significant risk factor for adverse outcomes in pregnant women with APS. Treatment with LMWH and aspirin was superior to aspirin alone. The creation of a global registry may be useful in improving the management of these patients.

Mechanisms of Ischemic Stroke in Patients with Cancer: A Prospective Study.

OBJECTIVE: The objective of this study was to examine the pathophysiology of ischemic stroke with cancer. METHODS: We conducted a prospective cross-sectional study from 2016 to 2020 at 2 hospitals. We enrolled 3 groups of 50 adult participants each. The main group included patients with active solid tumor cancer and acute ischemic stroke. The control groups included patients with acute ischemic stroke only or active cancer only. The patients with stroke-only and patients with cancer-only were matched to the patients with cancer-plus-stroke by age, sex, and cancer type, if applicable. The outcomes were prespecified hematological biomarkers and transcranial Doppler microemboli detection. Hematological biomarkers included markers of coagulation (D-dimer and thrombin-antithrombin), platelet function (P-selectin), and endothelial integrity (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], and soluble vascular cell adhesion molecule-1 [sVCAM-1]). Hematological biomarkers were compared between groups using the Kruskal-Wallis and Wilcoxon Rank-Sum tests. In multivariable linear regression models, we adjusted for race, number of stroke risk factors, smoking, stroke severity, and antithrombotic use. Transcranial Doppler microemboli presence was compared between groups using chi-square tests. RESULTS: Levels of all study biomarkers were different between groups. In univariate between-group comparisons, patients with cancer-plus-stroke had higher levels of D-dimer, sICAM-1, sVCAM-1, and thrombomodulin than both control groups; higher levels of thrombin-antithrombin than patients with cancer-only; and higher levels of P-selectin than patients with stroke-only. Findings were similar in multivariable analyses. Transcranial Doppler microemboli were detected in 32% of patients with cancer-plus-stroke, 16% of patients with stroke-only, and 6% of patients with cancer-only (p = 0.005). INTERPRETATION: Patients with cancer-related stroke have higher markers of coagulation, platelet, and endothelial dysfunction, and more circulating microemboli, than matched controls. ANN NEUROL 2021;90:159-169.

Delayed diagnosis of congenital thrombotic thrombocytopenic purpura in a patient with recurrent strokes.

Congenital thrombotic thrombocytopenic purpura (cTTP) is caused by ADAMTS13 mutations and associated with high risk of microvascular thrombosis. A 58 year old female had an ischemic stroke during hormonal fertility, and a TIA a year after. She suffered another stroke 18 years later while on warfarin. Four months after she developed severe thrombocytopenia, mild anemia, and increased LDH. Blood film showed schistocytes. She was hospitalized with presumptive TTP. ADAMTS 13 activity was undetectable without inhibitor. She developed another stroke and received plasma exchange. A homozygote ADAMTS 13 mutation was identified. Despite plasma, the ADAMTS13 activity remained < 10% and she had another stroke. Recombinant ADAMTS13 therapy was obtained through compassionate use. She receives weekly infusions maintaining ADAMTS13 trough levels above 10% without thrombotic recurrences. This case underscores the need to recognize cTTP as a cause of cryptogenic strokes, and the diagnostic value of the peripheral blood film. rADAMTS13 replacement may prevent recurrences.

Major hemorrhage and mortality in COVID-19 patients on therapeutic anticoagulation for venous thromboembolism.

We observed multiple fatal intracranial hemorrhages shortly after initiating therapeutic anticoagulation for treatment of venous thromboembolism (VTE) in COVID-19 patients suggesting increased anticoagulation risk associated with COVID-19. The objective of this study is to quantify risk of major hemorrhage in hospitalized COVID-19 patients on therapeutic anticoagulation for deep venous thrombosis (DVT) or pulmonary embolism (PE). Hospitalized patients with COVID-19 receiving therapeutic anticoagulation for DVT, PE or both at four New York City hospitals were evaluated for hemorrhagic complications. These were categorized as major (including fatal) or clinically relevant non-major according to the criteria of the International Society of Thrombosis and Haemostasis. Hemorrhagic complications were correlated with clinical and laboratory data, ICD-10 code diagnoses and type of anticoagulation treatment. Minor hemorrhages were excluded. Major/clinically relevant hemorrhages occurred in 36 of 170 (21%) hospitalized COVID-19 patients being treated with therapeutic anticoagulation for VTE including 4 (2.4%) fatal hemorrhages. Hemorrhage was 3.4 times more likely with unfractionated heparin 27/76 (36%) compared to 8/81 (10%) with low molecular weight heparin (p = 0.002). Multivariate analysis showed that major hemorrhage was associated with intubation (p = 0.04) and elevated serum LDH (p < 0.001) and low fibrinogen (p = 0.05). Increased risk of hemorrhagic complications in treating VTE in hospitalized COVID-19 patients should be considered especially when using unfractionated heparin, in intubated patients, with low fibrinogen and/or elevated LDH. Checking serum fibrinogen and LDH before initiating therapeutic anticoagulation and monitoring coagulation parameters frequently may reduce bleeding complications.

Prediction and Prevention of Cancer-Associated Thromboembolism.

Venous and arterial thromboembolism are prevalent, highly burdensome, and associated with risk of worse outcomes for patients with cancer. Risk for venous thromboembolism (VTE) varies widely across specific cancer subpopulations. The ability to predict risk of cancer-associated VTE is critical because an optimal thromboprophylaxis strategy is best achieved by targeting high-risk patients with cancer and avoiding prophylaxis in patients with cancer at low risk for VTE. A validated risk tool for solid tumors has been available for a decade. Newer tools have focused on specific populations, such as patients with multiple myeloma. Emerging studies continue to optimize risk prediction approaches in patients with cancer. Recent randomized trials have specifically addressed risk-adapted thromboprophylaxis using direct oral anticoagulants, and revised guidelines have included these new data to formulate recommendations for outpatient thromboprophylaxis. Implementation science approaches to enhance use of outpatient prophylaxis in the context of these guideline changes are under way. However, major knowledge gaps remain, including a lack of data for inpatient thromboprophylaxis in the cancer setting and a lack of formal tools for identifying risk of bleeding. This review describes optimal approaches to risk prediction and patient selection for primary pharmacologic thromboprophylaxis of cancer-associated VTE, addresses barriers to implementing these practices, and highlights strategies to overcome them. IMPLICATIONS FOR PRACTICE: Risk for venous thromboembolism (VTE) varies widely among patients with cancer. Individual risk can be determined using validated approaches. Inpatient and postsurgical thromboprophylaxis is more widely accepted. However, most patients with cancer develop VTE in the outpatient setting. Recent randomized trials have demonstrated benefit to risk-adapted outpatient thromboprophylaxis. High-risk patients may therefore be considered for outpatient thromboprophylaxis as recommended by recently updated guidelines. System-wide implementation approaches are necessary to improve compliance with prophylaxis.

Successful outcome with eculizumab treatment in a patient with antiphospholipid syndrome presenting with an unusual thrombotic storm.

Catastrophic Antiphospholipid Syndrome (CAPS) is a life-threatening complication of APS requiring complex management to optimize patient outcome. We describe a 54-year-old man with APS with history of splanchnic vein thrombosis, a Factor II G20210A heterozygote, autoimmune hemolytic anemia and thrombocytopenia. He developed sudden onset of severe flank pain due to spontaneous bilateral adrenal hemorrhage while on warfarin with a therapeutic INR. Despite unfractionated heparin and initial clinical improvement, severe thrombocytopenia developed requiring dexamethasone, rituximab, and romiplostim. Hospitalization was complicated further by thrombosis of the inferior vena cava, pulmonary embolism, and painful violaceous patches on his neck and ear cartilages. Punch biopsy of lesions revealed C5b-C9 deposition of small vessel thromboses. Although the inciting event for his thrombotic storm remains uncertain, anti-complement therapy with eculizumab provided rapid and durable lesion resolution. Eculizumab was discontinued after 6 months and patient remains in remission without recurrent thrombosis. This case provides insight on the management of CAPS, including the use of eculizumab.

Management of pregnancy in women with factor VII deficiency: A case series.

INTRODUCTION: Inherited factor VII deficiency is the most common autosomal recessive inherited bleeding disorder, with an estimated incidence of one per 500 000 cases in the general population. Bleeding manifestations correlate poorly with circulating FVII levels. During pregnancy, increases in FVII levels can occur in women with mild-moderate FVII deficiencies but not in those with severe deficiency. AIM: We present five pregnant patients with FVII deficiency and describe the management during their pregnancies and peripartum periods. METHODS: Retrospective analysis of six pregnancies in five women with FVII deficiency followed during pregnancy and delivery at an academic medical centre between January 2013 and December 2019. RESULTS: Of the five patients, two had severe, one with moderate and two with mild FVII deficiency. Early postpartum haemorrhage (PPH) occurred in two patients. One of the two severe FVII-deficient patients had PPH with a laceration at delivery despite replacement therapy with recombinant factor VII. The other PPH occurred in a patient with mild FVII deficiency who delivered twins by caesarean section under general anaesthesia. Neuraxial anaesthesia was utilized in only one woman with mild deficiency whose FVII level normalized at the end of the pregnancy. CONCLUSIONS: Management of delivery for women with FVII deficiency should be addressed on a case-by-case basis at centres with expertise in rare bleeding disorders, maternal foetal medicine and obstetric anaesthesiology. These management discussions should factor the patient's bleeding history, third trimester PT, FVII level, multiple gestation and mode of delivery.

Thrombotic risk factors in patients with antiphospholipid syndrome: a single center experience.

Patients with primary or secondary antiphospholipid syndrome (APS) have an increased risk of recurrent venous, arterial thrombosis and pregnancy complications. Therefore, determining thrombotic risk is important when individualizing antithrombotic therapy in patients with APS. To identify thrombotic risk factors in a cohort of APS patients. We conducted a retrospective review of APS patients who received care at a Hematology clinic of a university medical center from 2004 to 2017. Demographics, clinical features, antithrombotic therapy and thrombotic outcomes were collected. Time to event analysis identified clinical risk factors for thrombosis. The time varying effects of antithrombotic treatments on thrombosis outcome were analyzed. We identified 84 subjects with APS with a median age at diagnosis of 40.7 years [interquartile range [IQR] 33.5-57.6]. The majority were female (n = 63, 75%) and White (n = 45, 54%). Twenty-eight (33%) patients had concomitant autoimmune disease (AID) and of these, 15 (54%) had systemic lupus erythematosus. A thrombotic event occurred in 15 (18%) patients during a median follow-up of 48 months. A significantly higher rate of thrombotic events was observed in APS patients with AID compared to those without AID (hazard ratio (HR) 4.93, 95% CI 1.7-14.3, p = 0.04), and in black patients compared to whites (HR 5.94, 95% CI 1.1-32.1, p = 0.039). Patients on therapeutic anticoagulation regardless of type (warfarin, low molecular weight heparin or direct oral anticoagulants) were significantly less likely to have a recurrent thrombotic event compared to those on prophylactic anticoagulation (HR 0.11, 95% confidence interval [CI] 0.031-0.395, p = 0.001). However the numbers are too small to draw conclusions. Our study suggests that APS patients with concomitant AID and of Black race are at increased risk of recurrent thrombotic events.

Risk factors for and clinical management of venous thromboembolism during pregnancy.

Venous thromboembolism (VTE), which comprises deep vein thrombosis and pulmonary embolism, is one of the leading causes of non-obstetric maternal death in the United States. Physiologic and anatomic changes associated with pregnancy set the stage for a hypercoagulable state. In addition, other risk factors-including those associated with certain fetal characteristics such as low birth weight or stillbirth-have been correlated with an increased risk for VTE. Women with a personal or strong family history of VTE, as well as documented thrombophilia, represent a unique group in whom antepartum and/or postpartum prophylaxis can be considered. The choice of anticoagulant therapy for either treatment or prophylaxis in most cases is heparin, most commonly low-molecular-weight heparin. This is owing to the fact that vitamin K antagonists and the direct oral anticoagulants are contraindicated in pregnancy because of potential teratogenicity. With careful management and vigilant monitoring, appropriate anticoagulation can be used safely and effectively to improve patient outcomes.

Clinical Impact of Thrombophilia Screening in Young Adults with Ischemic Stroke.

OBJECTIVE: We evaluated the ability of genetic and serological testing to diagnose clinically relevant thrombophilias in young adults with ischemic stroke. METHODS: We performed a retrospective cohort study of patients aged 18-65 years diagnosed with acute ischemic stroke at a comprehensive stroke center between 2011 and 2015 with laboratory testing for thrombophilia. The primary outcome was any positive thrombophilia screening test. The secondary outcome was a change in clinical management based on thrombophilia testing results. Logistic regression was used to assess whether the prespecified risk factors of age, sex, prior venous thromboembolism, family history of stroke, stroke subtype, and presence of patent foramen ovale were associated with outcomes. RESULTS: Among 196 young ischemic stroke patients, at least 1 positive thrombophilia test was identified in 85 patients (43%; 95% CI, 36%-51%) and 16 (8%; 95% CI, 5%-13%) had a resultant change in management. Among 111 patients with cryptogenic strokes, 49 (44%) had an abnormal thrombophilia test and 9 (8%) had a change in management. After excluding cases of isolated hyperhomocysteinemia or methylenetetrahydrofolate reductase or Factor V Leiden gene mutation heterozygosity, the proportion of patients with an abnormal thrombophilia screen decreased to 24%. Prespecified risk factors were not significantly associated with positive thrombophilia testing or a change in management. CONCLUSIONS: Two-of-five young patients with ischemic stroke who underwent thrombophilia screening at our institution had at least 1 positive test but only one-in-twelve had a resultant change in clinical management. Neither cryptogenic stroke subtype nor other studied clinical factors were associated with a prothrombotic state.

Clinical presentations, risk factors, treatment and outcomes in patients with splanchnic vein thrombosis: a single-center experience.

Splanchnic vein thrombosis (SVT) is an uncommon form of venous thrombosis. Management can be challenging due to underlying conditions, increased bleeding risk, and lack of evidence from clinical trials. We sought to characterize the presentation and management of patients with SVT at a large tertiary hospital. A total of 43 patients' electronic medical records were reviewed. Median age at diagnosis was 43 (18-71). Sixteen patients had isolated portal vein thrombosis (37.2 %), and 16 (37.2 %) had thrombosis involving multiple splanchnic veins. Abdominal pain was the most common clinical presentation (67.4 %). Thrombophilia was present in 18 patients (41.9 %), nine had underlying liver disease (20.9 %) and seven had inflammatory bowel disease (16.3 %). Thirty-nine (90.7 %) patients were treated with anticoagulation, and 11(25.6 %) of these patients underwent interventional procedures. Thirty (69.8 %) patients remained on indefinite anticoagulation. Results of follow-up imaging at least 1 month after diagnosis were available for 29 patients; imaging showed chronic, stable thrombosis in 14 patients (48.3 %), resolution of thrombosis in 13 patients (44.8 %) and asymptomatic progression in two patients (6.9 %). Recurrent thrombosis occurred in four patients (9.3 %). Major bleeding occurred in eight patients who received anticoagulation (18.6 %), including fatal subdural hematoma in one patient. In this cohort of patients managed by hematologists and gastroenterologists, the majority of patients were treated with anticoagulation. Interventional procedures were higher than in previously reported series. Our study strongly supports the interdisciplinary management of splanchnic venous thrombosis.

Recombinant Human Antithrombin in Pregnant Patients with Hereditary Antithrombin Deficiency: Integrated Analysis of Clinical Data.

OBJECTIVES: The purpose of this analysis was to evaluate the use of recombinant human antithrombin (rhAT) in preventing venous thromboembolism (VTE) in pregnant patients with hereditary AT deficiency (HATD). STUDY DESIGN: Data from two clinical trials were pooled. Dosing of rhAT was based on body weight and baseline AT activity, started up to 24 hours before scheduled induction or cesarean delivery, or at the onset of labor. RESULTS: A total of 21 pregnant HATD patients were enrolled. Mean rhAT therapy duration was 4.3 days and dose was 245.1 IU/kg/day. All patients achieved target mean AT activity (80-120% of normal) during rhAT therapy. There were no confirmed VTEs during rhAT treatment or within 7 ( ± 1) days after dosing. Two VTE events (one deep vein thrombosis and one pulmonary embolism) occurred 11 and 14 days after discontinuation of rhAT, in patients managed with prophylactic doses of heparin or low-molecular-weight heparin following delivery. CONCLUSION: rhAT was safe and effective in pregnant HATD patients when administered during the peripartum period, the period of highest VTE risk and a time when anticoagulation therapy is normally withheld. Pregnant HATD patients may benefit from therapeutic, rather than prophylactic, doses of anticoagulation after delivery to protect against postpartum VTE.

Role of novel anticoagulants for patients with mechanical heart valves.

The introduction of the target-specific oral anticoagulants (TSOACs) has led to a major shift in the management of patients at risk for thrombosis. The landscape continues to evolve as the evidence regarding their efficacy and safety in various clinical situations emerges. Antithrombotic therapy for thromboprophylaxis in patients with mechanical heart valves is challenging. To date, the RE-ALIGN trial comparing dabigatran etexilate to warfarin is the only randomized controlled study in this patient population. The higher risk of thromboembolic and bleeding events in the group of patients who received dabigatran compared with warfarin reinforced current guidelines recommending against the use of TSOACs in patients with mechanical heart valves. However, additional studies are needed to find suitable alternatives to vitamin K antagonists in this unique patient population.

Hereditary Antithrombin Deficiency Pilot Project Registry from the American Thrombosis and Hemostasis Network (ATHN).

BACKGROUND: Patients with hereditary antithrombin deficiency (HAD) have an increased risk of venous thromboembolism (VTE). ATHN 12: HAD Pilot Project established a registry to collect data on patients with HAD to inform current practice and serve as a platform to design a multicenter global registry for patients with HAD. METHODS: The HAD registry was designed in 2020 to identify 100 patients with HAD receiving care at ATHN-affiliated centers. Demographics, type of HAD, thrombotic events, risk factors, anticoagulants, and AT concentrate administration were recorded. RESULTS: Ninety-four (94) patients were included; 65% were females; 51% had type 1 HAD. Mean age at diagnosis was 26 years (SD18); 61% had VTE: 55% deep vein thrombosis and 27% pulmonary embolisms. Eight patients had arterial thrombosis. Recurrent thrombosis occurred in 58.6% patients: (44.8%) despite anticoagulation. The main risk factor for thrombosis in females was estrogen. Direct oral anticoagulants were prescribed in 30%, heparin in 34%, and warfarin in 32%. There were 139 pregnancies. Low molecular weight heparin was administered in 33% and AT concentrate in 19% and 11% prior and post-delivery, respectively. Twelve patients developed thrombosis in pregnancy. Seventy-nine patients underwent 239 surgeries or procedures, mainly gastrointestinal and vascular, respectively. Overall, 35% participants received AT concentrate without adverse events. CONCLUSIONS: In ATHN 12, VTE was the predominant manifestation, frequently recurrent. There was a trend towards using DOACs. LMWH was administered in one-third of pregnancies and AT concentrate in one-fifth without adverse events. These data should encourage prospective studies to optimize the management of these patients.

Lingual thrombosis in a woman with antiphospholipid syndrome.

A 28-year-old woman, 34 weeks pregnant, with previously diagnosed antiphospholipid syndrome, presents with vesicular tongue lesions treated as herpes outbreak and new onset of preeclampsia. Tongue biopsy preformed postpartum after induction of labor for preeclampsia reveals tongue infarction.

Corrigendum to 'The Hemophilia Joint Health Score version 2.1 Validation in Adult Patients Study: A multicenter international study' [Research and Practice in Thrombosis and Haemostasis, 6/2, (2022) e12690].

[This corrects the article DOI: 10.1002/rth2.12690.].

Onset of labor and use of analgesia in women using thromboprophylaxis with 2 doses of low-molecular-weight heparin: insights from the Highlow study.

BACKGROUND: Peripartum management of women using low-molecular-weight heparin (LMWH) varies widely. Minimum time intervals are required between LMWH injection and neuraxial procedure, and they differ by dose. OBJECTIVES: The objective of this study was to describe the onset of labor and use of analgesia in women using LMWH and to compare practices between intermediate-dose and low-dose LMWH. METHODS: In the Highlow study (NCT01828697), 1110 women were randomized to intermediate-dose or low-dose LMWH and were instructed to discontinue LMWH when labor commenced unplanned or 24 hours prior to planned delivery. The required time interval since last injection to receive a neuraxial procedure was ≥24 hours for intermediate-dose LMWH or ≥12 hours for low-dose LMWH. RESULTS: In total, 1018 women had an ongoing pregnancy for ≥24 weeks. Onset of labor was spontaneous in 198 of 509 (39%) women on intermediate-dose LMWH and in 246 of 509 (49%) on low-dose LMWH. With unplanned onset, a neuraxial procedure was performed in 37% on intermediate-dose and in 48% on low-dose LMWH (risk difference -11%, 95% CI -20% to -2%). Based on time interval, 61% on intermediate-dose and 82% on low-dose LMWH were eligible for a neuraxial procedure. With planned onset, 68% on intermediate-dose and 66% on low-dose LMWH received a neuraxial procedure, whereas 81% and 93%, respectively, were eligible for a neuraxial procedure (risk difference -13%, 95% CI -18% to -8%). CONCLUSION: With spontaneous onset of labor, neuraxial procedures were performed less often in women using intermediate-dose LMWH. Irrespective of onset, fewer women on intermediate-dose LMWH than those on low-dose LMWH were eligible for neuraxial procedures based on required time intervals since the last LMWH injection.