Treasure to the mother and threat to the fetus: case report of warfarin-associated fetal intracranial hemorrhage and review of literature.

In patients with mechanical heart valve protheses, warfarin is usually recommended because of its exceptional anticoagulation effects. However, warfarin can cross the placenta, leading to teratogenicity and even catastrophic hemorrhage in the fetus. The present article describes a case of warfarin-associated fetal intracranial hemorrhage. The patient was a woman in her early 30s. At the age of 11 years, she had undergone aortic valve replacement (mechanical) for aortic regurgitation. Since then, she had been taking oral warfarin. During her pregnancy, her prothrombin time-international normalized ratio was maintained between 1.5 and 2.5. At 35 weeks of gestation, fetal ultrasonography revealed an intracranial mass in the left hemisphere. An emergency cesarean section was performed because fetal intracranial hemorrhage was suspected. A male infant was delivered with a 1- 5-, and 10-minute Apgar score of 1, 5, and 7, respectively. Cranial computed tomography revealed multiple hemorrhage sites with newly emerged bleeding spots. In patients with mechanical heart valve protheses, obstetricians face the dilemma of individual-patient differences and the difficulty of intensive monitoring of the coagulation parameters in the fetus. Tailor-made anticoagulation therapy and a more intensive ultrasonic monitoring strategy, even that involving regular magnetic resonance imaging, are necessary in these patients.

Association of thrombophilia prospective detection with hemocompatibility related outcomes in left ventricular assist device patients.

INTRODUCTION: Inherited thrombophilias represent a concerning risk factor due to a proclivity to an aberrant clot formation. However, in patients with left ventricular assist device (LVAD), their impact on bleeding and thrombotic complications remains still poorly understood. The aim of the present study was to evaluate the effect of thrombophilic mutation directed anticoagulation therapy on adverse clinical outcomes in LVAD patients. MATERIALS AND METHODS: About 138 consecutive patients indicated for LVAD implant (HeartMate II, Abbott, Plymouth, USA) were prospectively screened for three major thrombophilic mutations: factor II (prothrombin), factor V Leiden, and homozygous methylenetetrahydrofolate reductase (MTHFR). Subsequently, discordant individualized anticoagulation targets of INR 2.5-3.0 in thrombophilia positive and INR 1.8-2.2 in negative patients were established; notably without anti-platelet agents given the center standard of care. RESULTS: Mean age was 50 ± 12.7 years, 83% male. Mean duration of support was 464.5 days (SD 482.9; SEM 41.1) and median of 310 days (IQR 162; 546). Full thrombophilia positive cohort analysis has not revealed any significant impact on event free survival. In contrast, detailed analysis of specific thrombophilias subsets has revealed Factor II prothrombin mutation as a significant predisposition for the pump thrombosis risk (SHR 10.48; p = 0.001) despite more aggressive prespecified anticoagulation target. Moreover, the incidence of bleeding events in prothrombin group was also significantly increased (SHR 6.0; p = 0.03). CONCLUSIONS: Our observations suggest that specific thrombophilias in LVAD patients may pose different intensity predisposition for thrombotic complications. Factor II (prothrombin) positive mutation was identified as significant risk factor associated with the pump thrombosis.

Anticoagulation strategy in a patient on the HeartMate III® left ventricular assist device with acquired von Willebrand syndrome and recurring gastrointestinal bleeding episodes: sometimes less is more.

Acquired von Willebrand syndrome is a frequently encountered complication of continuous flow ventricular assist devices, which may lead to clinically relevant bleeding in up to 30% of patients after continuous flow ventricular assist device implantation. As standard anticoagulation strategies may be detrimental, individualized treatment is called for, as described in our patient on the HeartMate III® left ventricular assist device.

Case Analysis o f Clinical Pharmacists Participating in Warfarin Individualized Anticoagulation Therapy for a Patient with Lo- wer Extremity Venous Thrombosis Complicated with Pulmonary Arterial Thromboembolism / 中国药房

OBJECTIVE： To investigate the role of clinical pharmacists in the individual anticoagulation of warfarin for the patients with lower extremity venous thrombosis （LEVT） and pulmonary arterial thromboembolism （PATE）. METHODS： Clinical pharmacists participated in individual anticoagulation of warfarin for the patients with LEVT and PATE. It was suggested to detect the gene type of the patient. According to the results of gene test [cytochrome P450 （CYP）2C9*1*1 and vitamin K epoxide reductase complex subunit Ⅰ] and the dose recommended by FDA based on the patient’s gene， the initial dose of warfarin （3.125 mg，once a day） was determined according to the patient’s living habits， height and body mass. Then the maintenance dose of warfarin （the maintenance dose of warfarin was 2.5 mg and 3.125 mg， once a day， alternately taken every other day） was calculated according to the warfarin maintenance dose prediction formula established by Warfarin Pharmaeogenetics Consortium. Pharmaceutical monitoring was conducted， such as INR， prothrombin time and bleeding event monitering. RESULTS： Physicians adopted the suggestion of clinical pharmacists. The maintenance dose of warfarin was 2.5 mg and 3.125 mg， once a day， alternately taken every other day. It was suggested to give Flucloxacillin sodium injection which had less influence on warfarin. The patient recovered well and was discharged. CONCLUSIONS： Based on pharmacogenomics， clinical pharmacists participate in the formulation of individualized anticoagulant regimens for patients， which promote TNR ralue of patients， reduce the risk of early postoperative thromboembolism， and further ensure the safety of drug use in patients.

Individualized anticoagulation versus empirical anticoagulation therapy after cardiac valve replacement in Uygur patients: A randomized controlled trial / 中国胸心血管外科临床杂志

@#Objective    To investigate whether the individualized anticoagulation therapy based on CYP2C9 and VKORC1 gene is superior to empirical anticoagulation therapy after artificial heart valve replacement surgery in Uygur patients. Methods    From December 2012 to December 2015, 210 Uygur patients who underwent artificial heart valve replacement surgery at the First Affiliated Hospital of Xinjiang Medical University were randomly assigned to a genetic anticoagulation therapy group (group A, n=106, 41 females and 65 males, aged 44.7±10.02 years) or an empirical anticoagulation therapy group (group B, n=104, 47 females and 57 males, aged 45.62±10.01 years) according to the random number table. CYP2C9 and VKORC1 genotypes were tested in the group A and then wafarin of administration in anticoagulation therapy was recommended. Patients in the group B were treated with conventional anticoagulation. Patients in both groups were followed up for 1 month and coagulation function was regularly tested. Results    The percentage of patients with INR values of 1.8-2.5 after 4 weeks warfarin anticoagulation treatment in the group A was higher than that in the group B (47.1% vs. 32.7%, P=0.038). The rate of INR≥3.0 in the warfarin anticoagulation therapy period in the group A was lower than that in the group B (21.6% vs. 26.5%, P=0.411). The time to reach the standard INR value and the time to get maintenance dose were shorter in the group A compared with the group B (8.80±3.07 d vs.   9.26±2.09 d, P=0.031; 14.25±4.55 d vs. 15.33±1.85 d, P=0.032). Bleeding occured in one patient in the group A and three patients in the group B (P=0.293). Embolic events occured in three patients in the group A and five patients in the group B (P=0.436). Conclusion    Compared with the empirical anticoagulation, the genetic anticoagulation based on wafarin dosing model can spend less time and make more patients to reach the standard INR value. However there is no significant difference between the two groups in the ratio of INR≥3.0, bleeding and embolic events in the warfarin anticoagulation therapy.