Hemostasis-related gene polymorphisms and their epistatic relationship in women with idiopathic infertility A numerous factor can cause infertility, but around one of four reproductive failure cases remain unexplained and diagnosed as idiopathic infertility. In the past few decades, analysis of gene polymorphisms takes a significant place in pathogenesis of infertility. The aim of this study was to evaluate the possible role of hemostasis-related gene polymorphisms in unexplained infertility. The study includes 117 female patients with idiopathic infertility and 130 fertile women with at least one born child. Eight polymorphisms important for hemostasis (ITGB3 1565T>C, FV 1691G>A, FII 20210G>A, MTHFR 677C>T and 1298A>C, ATIII 786G>A, PAI-14G/5G and ACE I/D) were genotyped by real-time PCR system. The frequencies of alleles and genotypes of examined polymorphisms were analyzed in SPSS statistical program, whereas gene interactions were identified using the GMDR software. Examination of etiological factors has shown that family history is a significant factor in assessing individual risk for infertility. The alleles and genotypes frequency of FV 1691G>A and FII 20210G>A polymorphisms were statistically different between control and patient group leading to a greater risk for infertility. The analysis of epistatic relationship between examined hemostasis-related gene polymorphisms identified more complex high-risk genotypes associated with infertility. Our results suggest that positive family history could be important predictive factor for fertility problems, pointing to the potential hereditary basis of this condition. Polymorphisms FVL and FII prothrombin are independent risk factors for idiopathic infertility, whereas multilocus interactions approach should be taken into consideration for the future research.

Measuring high on-treatment platelet reactivity in clinical practice; should we use a panel of platelet function tests? High on-treatment platelet reactivity (HPR) on P2Y12-inhibitors in patients treated with dual antiplatelet therapy is strongly associated with adverse ischaemic events. Studies have shown conflicting results with regard to the correlation and agreement between the different tests. Several assays are available to establish HPR. A composite advice based on more than one test might be a better way to identify HPR patients. To compare HPR rates and agreement between individual platelet function tests and a panel of three tests In our large percutaneous coronary intervention centre, all patients who suffered a stent thrombosis were invited back to a dedicated clinic. Platelet function testing was performed in all patients and matched control patients. HPR rates were compared between individual tests and with a composite comprised of three tests. A total of 242 patients were included, of whom in 193 patients all tests were available. HPR rates ranged from 14.6% [VerifyNow cut-off >235 platelet reactivity units (PRU)] to 49.7% (Vasodilator-Stimulated Phosphoprotein Assay). HPR according to the composite advice (≥2 out of 3 tests indicating HPR) was present in 29.8% of patients. The best correlation with the composite advice was observed with light transmittance aggregometry (kappa = 0.78) and VerifyNow (lower cut-off >208 PRU; kappa = 0.68). VerifyNow with cut-off more than 235 PRU identified the smallest proportion of patients with HPR, whereas Vasodilator-Stimulated Phosphoprotein Assay seemed to ‘over-identify’ HPR. In this real life patient cohort, a large variability was observed between four different platelet function tests. The use of a composite advice based on three tests is a promising alternative.

The predictive value of stress hyperglycemia on thrombus burden in nondiabetic patients with ST-segment elevation myocardial infarction It is established that hyperglycemia directly effects the platelet functions and fibrin structure. In this study, we aimed to investigate the predictive value of hyperglycemia on thrombus burden in nondiabetic patients with ST-segment elevation myocardial infarction (STEMI) who underwent to primer percutaneous coronary intervention (PPCI). We enrolled 619 nondiabetic patients with STEMI who received PPCI. Patients were divided two groups according to thrombus burden. Stress hyperglycemia was determined as blood glucose concentration more than 180 mg/dl and angiographic coronary thrombus burden was scored based on thrombolysis in myocardial infarction thrombus grades. Patients with thrombus grades 4 were defined as large thrombus burden (LTB), patients with thrombus burden less than thrombus grades 4 were defined as small thrombus burden. A total of 68 (11.0%) STEMI patients had stress hyperglycemia, while 223 (36.0%) patients had LTB. Sex, the prevalence of hypertension, smoking, and dyslipidemia were not different between the thrombus burden groups (P > 0.05 for all parameters). Compared with the patients with small thrombus burden, the patients with LTB were had significantly higher admission blood glucose concentrations (135 ± 39.1 mg/dl vs. 145.9 ± 43.1, P = 0.002, respectively). The multivariate logistic regression analysis demonstrated that stress hyperglycemia is an independent predictor of LTB (odds ratio: 3.025, confidence interval 1.200–7.622, P = 0.019). Admission hyperglycemia is associated with the LTB which cause adverse cardiac outcomes. Hyperglycemia may play a role on thrombus development.

Rare clotting factor deficiency among Sudanese children Rare clotting factor (F) deficiency is a deficiency of one or more of coagulation factors other than FVIII, FIX and vonWillebrand (FI, FII, FV, FV + FVIII, FVII, FIX, FX, FXI and FXIII) that cause bleeding disorders and are inherited as autosomal recessive. Descriptive study was conducted in Hemophilia Centre, Khartoum, Sudan. The medical files of pediatric patients presented to the center were reviewed retrospectively. Forty-seven patients (male : female ratio = 1.2 : 1) were included. The majority (93.6%) have parental history of consanguinity and around one third (31.9%) have family history of bleeding disorder. FV deficiency was the most common deficient factor (36.2%) followed by FI deficiency (23.4%) and FX111 deficiency (21.3%). Bruising (46.8%) and epistaxis (25.5%) were the most common presenting complains. FV deficiency mainly presented with cutaneous ecchymosis (47.1%). FI deficiency presented with umbilical bleeding (45.5%) and FXIII presented with cutaneous ecchymosis (50%). Rare clotting factor deficiency is an existing disease in Sudan with the male : female ratio was 1.2 : 1. FV deficiency, FI deficiency, FXIII deficiency were the common deficiency encountered.

Application of thrombelastography in primary total knee and total hip replacement: a prospective 87 patients study Thrombelastography (TEG) parameters and prothrombin time (PT), activated partial thromboplastin time (APTT) are compared and analysed. According to change of TEG parameters and assessment of haemostatic state of each patient, we try to explore the feasibility of individualized anticoagulant therapies. 87 people with hip or knee diseases awaiting arthroplasty were recruited. Haemoglobin levels and TEG parameters including R, K, α-angle, maximum amplitude, coagulation index were assessed in perioperative period. PT and APTT were assessed preoperatively. For 65 patients with normal TEG parameters, PT and APTT, we use tranexamic acid (TXA) to reduce blood loss during operation. As hypercoagulability group, 12 patients awaiting unilateral total knee arthroplasty with hypercoagulable state assessed by TEG parameters or risks for venous thromboembolism received daily 10-mg rivaroxaban until 24 h preoperatively and did not receive TXA during operation. All patients received intravenous administration of argatroban after 8 h postoperatively until day 3 and oral administration of rivaroxaban (10 mg) subsequently to prevent deep vein thrombosis or/and pulmonary embolism until 35 days postoperatively. TEG parameters have significant relationships with fibrinogen, platelet and APTT. The number of patients with abnormal haemostatic state assessed by TEG parameters is higher than that assessed by PT, APTT. TEG show hypercoagulability develops throughout perioperative period. There was no significant difference in haemoglobin concentration between hypercoagulability group and normal group in patients receiving unilateral total knee arthroplasty. TEG have higher sensitivity of perioperative abnormal haemostatic state than PT, APTT in primary arthroplasty. For patients with hypercoagulability, individualized anticoagulant therapies such as preoperative administration of rivaroxaban and not using TXA in operation is safe and effective.

Development of an inhibitor in a child with severe hemophilia B: treatment with immunosuppression and an extended desensitization protocol Development of neutralizing alloantibodies in hemophilia B is a less common, but clinically challenging phenomenon. Novel therapeutics for hemophilia B have recently been developed and reports of clinical experience with these agents outside of clinical trials are needed. We report development of an inhibitor in a child with severe hemophilia B, and subsequent immune tolerance induction using an extended desensitization protocol with the addition of immunosuppression. This case highlights successful management of a rare complication in a rare bleeding disorder and the need for additional investigation into this infrequent and clinically challenging occurrence.

Thrombopoietin receptor agonists as second-line therapy in splenectomy-eligible persistent immune thrombocytopenia: a case series Thrombopoietin receptor agonists (TPO-RA) are currently approved to treat chronic immune thrombocytopenia (ITP) but there is increasing interest in considering these drugs earlier during the course of the disease. We present six patients with primary ITP resistant to corticosteroids and intravenous immunoglobulins, who received TPO-RA in the persistent phase and then underwent splenectomy in the chronic phase. Eltrombopag was administered as a second-line therapy in four patients, whereas two patients received romiplostim. Five out of six patients rapidly reached response or complete response (four and one, respectively) and steroid suspension. In one case, remission was obtained with steroid and TPO-RA. No significant side effects were reported. After splenectomy, complete response and response was reached in four and two patients, respectively. One relapse was recorded, rescued by steroid and eltrombopag. Postsplenectomy complication was registered in one patient (grade 4 intra-abdominal bleeding). TPO-RA could be a valuable choice in ITP patients in persistent phase candidates to splenectomy.

Prolonged activated partial thromboplastin time due to plasma prekallikrein deficiency: a case study and literature review on its clinical significance Activated partial thromboplastin time is a test assessing the intrinsic and common pathways of the coagulation cascade. We presented an asymptomatic case with isolated activated partial thromboplastin time prolongation. After excluding coagulation factor deficiency and lupus anticoagulant, the patient was diagnosed with plasma prekallikrein (PPK) deficiency. We reviewed the literature regarding effects of PPK deficiency which could have both antithrombotic and prothrombotic effects. At the moment, research supports that PPK deficiency in healthy adults rarely causes bleeding as it is not a major contributor of hemastasis; whereas in adults with multiple comorbidities or with predominant systemic inflammation, effects of PPK deficiency remain debatable. Further research is needed to clarify impacts of PPK deficiency in clinical settings.

Antithrombin concentrate during pregnancy in congenital antithrombin deficiency: a single-center experience Pregnancy carries a high risk of thromboembolic complications, especially in the postpartum period. This risk is particularly high in women with inherited thrombophilias, among these antithrombin deficiency seems to carry the highest risk. In this case, the use of low molecular weight heparin (LMWH) is recommended, while the use of antithrombin concentrate is controversial. We report our experience of seven pregnancies occurred in five women: two, with a personal and familiar history negative for venous thromboembolism, were treated with LMWH during pregnancy and antithrombin concentrate immediately before and after the delivery. The other three women had a personal and familiar history positive for venous thromboembolism and were treated with LMWH and antithrombin concentrate during all the pregnancy and the postpartum period. No thromboembolic or hemorrhagic complications were observed in both groups, demonstrating that our strategy could be safe and effective.