Various inherited traits contribute to the overall risk of venous thromboembolism (VTE). In addition, the epidemiology of thrombophilia in the East-Asian VTE population remains unclear; thus, we aimed to assess the proportion of hereditary thrombophilia via a meta-analysis. Publications from PubMed, EMBASE, web of science, and Cochrane before December 30, 2022, were searched. Studies from Japan, Korea, China, Hong Kong, Taiwan, Singapore, Thailand, Vietnam, Myanmar, and Cambodia were included. Congenital thrombophilia was described as diseases including protein C (PC) deficiency, protein S (PS) deficiency, antithrombin (AT) deficiency, factor (F)V Leiden (FVL), and prothrombin G20210A mutations. Studies were selected by 2 reviewers for methodological quality analysis. A random-effects model was used for the meta-analysis, assuming that estimated effects in the different studies are not identical. Forty-four studies involving 6453 patients from 7 counties/regions were included in the meta-analysis. The prevalence of PC, PS, and AT deficiencies were 7.1%, 8.3%, and 3.8%, respectively. Among 2924 patients from 22 studies, 5 patients were carriers of FVL mutation. Among 2196 patients from 10 studies, 2 patients were carriers of prothrombin G20210A mutation in a Thailand study. The prevalence of PC, PS, and AT deficiencies was relatively high, while a much lower prevalence of FVL and prothrombin G20210A mutations were identified in East-Asian patients with VTE. Our data stress the relative higher prevalence of PC, PS, and AT deficiencies for thrombophilia in the East-Asian VTE population.

In this guideline, recurrent miscarriage has been defined as three or more first trimester miscarriages. However, clinicians are encouraged to use their clinical discretion to recommend extensive evaluation after two first trimester miscarriages, if there is a suspicion that the miscarriages are of pathological and not of sporadic nature. Women with recurrent miscarriage should be offered testing for acquired thrombophilia, particularly for lupus anticoagulant and anticardiolipin antibodies, prior to pregnancy. [Grade C] Women with second trimester miscarriage may be offered testing for Factor V Leiden, prothrombin gene mutation and protein S deficiency, ideally within a research context. [Grade C] Inherited thrombophilias have a weak association with recurrent miscarriage. Routine testing for protein C, antithrombin deficiency and methylenetetrahydrofolate reductase mutation is not recommended. [Grade C] Cytogenetic analysis should be offered on pregnancy tissue of the third and subsequent miscarriage(s) and in any second trimester miscarriage. [Grade D] Parental peripheral blood karyotyping should be offered for couples in whom testing of pregnancy tissue reports an unbalanced structural chromosomal abnormality [Grade D] or there is unsuccessful or no pregnancy tissue available for testing. [GPP] Women with recurrent miscarriage should be offered assessment for congenital uterine anomalies, ideally with 3D ultrasound. [Grade B] Women with recurrent miscarriage should be offered thyroid function tests and assessment for thyroid peroxidase (TPO) antibodies. [Grade C] Women with recurrent miscarriage should not be routinely offered immunological screening (such as HLA, cytokine and natural killer cell tests), infection screening or sperm DNA testing outside a research context. [Grade C] Women with recurrent miscarriage should be advised to maintain a BMI between 19 and 25 kg/m2 , smoking cessation, limit alcohol consumption and limit caffeine to less than 200 mg/day. [Grade D] For women diagnosed with antiphospholipid syndrome, aspirin and heparin should be offered from a positive test until at least 34 weeks of gestation, following discussion of potential benefits versus risks. [Grade B] Aspirin and/or heparin should not be given to women with unexplained recurrent miscarriage. [Grade B] There are currently insufficient data to support the routine use of PGT-A for couples with unexplained recurrent miscarriage, while the treatment may carry a significant cost and potential risk. [Grade C] Resection of a uterine septum should be considered for women with recurrent first or second trimester miscarriage, ideally within an appropriate audit or research context. [Grade C] Thyroxine supplementation is not routinely recommended for euthyroid women with TPO who have a history of miscarriage. [Grade A] Progestogen supplementation should be considered in women with recurrent miscarriage who present with bleeding in early pregnancy (for example 400 mg micronised vaginal progesterone twice daily at the time of bleeding until 16 weeks of gestation). [Grade B] Women with unexplained recurrent miscarriage should be offered supportive care, ideally in the setting of a dedicated recurrent miscarriage clinic. [Grade C].

The association between heritability of venous thromboembolism (VTE) and thrombophilia was first reported clinically in 1956, later followed by the first description of a congenital cause of hypercoagulability-antithrombin deficiency-in 1965. Since then, our knowledge of hereditary causes of hypercoagulability, which may predispose carriers to VTE has improved greatly. Novel genetic defects responsible for severe thrombophilia have been recently identified and we have learned that a wide range of interactions between thrombophilia and other genetic and acquired risk factors are important determinants of the overall individual risk of developing VTE. Furthermore, therapeutic strategies in thrombophilic patients have benefited significantly from the introduction of direct oral anticoagulants. The present review is an overview of the current knowledge on the mechanisms underlying inherited thrombophilia, with a particular focus on the latest achievements in anticoagulation protocols and prevention strategies for thrombosis in carriers of this prothrombotic condition.

To summarize the literature assessing the safety and efficacy of direct oral anticoagulants (DOACs) for the acute treatment and secondary prevention of venous thromboembolism (VTE) in select patients with hypercoagulable disorders. An electronic PubMed literature search was conducted from January 2010 to July 2020 using the following keywords: DOAC, rivaroxaban, apixaban, dabigatran, edoxaban, thrombophilia, cancer, antiphospholipid syndrome, protein C deficiency, protein S deficiency, antithrombin deficiency, factor V Leiden, prothrombin G20210A gene mutation, congenital thrombophilia, hypercoagulable, hereditary thrombophilia, acquired thrombophilia. Articles were included if they reported clinical outcomes associated with cancer-associated VTE, antiphospholipid syndrome (APS), and other hereditary thrombophilias. The safety and efficacy of using a DOAC is highly dependent on the type of hypercoagulable disease state. Current trials support the use of edoxaban, rivaroxaban, and apixaban for the treatment of cancer-associated thrombosis (CAT), with apixaban being preferred because of lower bleeding rates compared with standard of care. The use of DOACs, especially rivaroxaban, have been associated with worse outcomes in patients with APS, whereas data on DOAC use in hereditary thrombophilia remains scarce and limited to low-risk patients. This review evaluates the literature assessing the safety and efficacy of DOACs in patients with various hypercoagulable disorders. The current body of evidence supports the use of select DOACs for the treatment of CAT. In contrast, DOAC use in patients with APS and hereditary thrombophilia should be avoided at this time.

The modified systemic to pulmonary artery shunt (mSPS) is an effective palliative procedure in children with cyanotic congenital heart disease (CCHD) who are not suited for total correction. Early graft failure related to hereditary thrombophilic disorder is one cause of mortality. The aim of this study is to compare the clinical outcomes and rate of graft failure after mSPS in cyanotic infants with hereditary thrombophilia using bovine mesenteric venous graft (BMVG) and polytetrafluoroethylene (PTFE). 60 cyanotic patients (28 neonates, mean age 19 ± 11.3 days; range 1 to 27) who had thrombophilic risk factors were divided into 2 groups: BMVG (n = 30) and PTFE (n = 30). Preoperative thrombophilic factors were measured for each patient. The most common thrombophilic factors were protein C and S deficiency and Factor V Leiden mutation. We also investigated D-dimer, positivity of prothrombin G20210A, factor XII and antithrombin III deficiency, and homocysteinemia in both groups. The mean age of patients was 4.6 ± 1.09 months (range 1 day to 6 months) in the BMVG group and 3.9 ± 1.02 months (range 2 days to 9 months) in the PTFE group (P = .67). mSPS procedures were performed via left thoracotomy (n = 19 in the BMVG group and n = 22 in the PTFE group) or right anterior thoracotomy (n = 3 in the BMVG group and n = 3 in the PTFE group). Median sternotomy was performed to create a central shunt in 8 neonates in the BMVG group. In the PTFE group, we performed a central shunt in 5 patients via median sternotomy. Low molecular weight heparin in combination with acetylsalicylic acid (aspirin) were administered after surgery in both groups. The patients received aspirin combined with warfarin (Coumadin) after being discharged from hospital. We performed revision surgery to observe whether any patient had a significant drop in saturation with inaudible mSPS murmur. 7 patients died early after surgery (n = 2 in the BMVG group [6.6%] and n = 5 in the PTFE group [16.5%]; P = .022). 53 patients were discharged home in good clinical condition. Early graft thromboses were observed in 2 patients in the BMVG group (6.6%) and 8 patients in the PTFE group (26.6%) (P = .001). In a case from the BMVG group, the reason for graft thrombosis was entanglement of the graft. Revision surgery was performed successfully without any complication. Cil et collegues has been reported a successful percutaneous balloon angioplasty after an acute thrombosis of BMVG previously [Cil 2010]. In another patient who had acute BMVG thrombosis, we performed transluminal graft angioplasty using successful thrombolytic administration in the catheterization laboratory. There were no complications due to graft materials such as hematoma, seroma, or infection in the BMVG group. Bleeding from the needle hole was seen in 1 patient in the BMVG group. PTFE thrombosis developed in 3 patients within 24 hours (10%). We detected total or partial PTFE graft thrombosis in 5 patients during the follow-up period (20%). Revision surgeries in 3 patients were performed immediately after diagnosis. Transluminal balloon angioplasty combined with thrombolysis was performed in infants with partial or total PTFE occlusion in 5 patients. In the PTFE group, perigraft seroma (n = 5 [16.6%)] and hematoma (n = 2 [6.6%]) were detected. We performed revision surgery because of bleeding from the needle hole in 3 patients in the PTFE group (10%) in the early period after surgery. We detected a graft infection in 1 patient (3.3%) 6 months after surgery in the PTFE group. The rate of overall complications including pseudoaneurysm, seroma formation, graft infection, or partial or total graft occlusion in the early and follow-up periods was 6.6% in the BMVG group and 53.3% in the PTFE group (P = .0001). The rate of freedom from shunt failure was 92.6% ± 2.1% and 76.2% ± 4.8% during follow-up in BMVG and PTFE groups, respectively (P = .034). The rate of shunt-related mortality was 10.7% (n = 3) in the BMVG group and 20% in the PTFE group (P = .01). Regular physical examinations, transcutaneous oxygen saturation, and echocardiographic study were performed for shunt control during follow-up. Shunt occlusion or thrombosis was not seen in the BMVG group; 5 patients in the PTFE group (20%) had shunt occlusion during follow-up (P = .001). Our study shows that BMVG, as a biological material, may be used as an alternative material for creating mSPS. It decreases postoperative life-threatening complications after shunt procedures, including graft thrombosis, bleeding from the needle hole, perigraft hematoma, and seroma in patients with hereditary thrombophilia. To our knowledge, we report the first clinical comparison of the 2 grafts in our case series with thrombophilic risk factors.