Evidence-Based Minireview: Should warfarin or a direct oral anticoagulant be used in patients presenting with thrombosis in the splanchnic or cerebral veins?

Abstract Case 1: A 23-year-old female third-year medical student who has no medical history seeks treatment for abdominal distention. She takes an estrogen-containing birth control pill and does not smoke or consume alcohol. Family history is unremarkable. Physical examination is significant for abdominal distention, and an abdominal fluid wave is detected. Complete blood count is normal. Imaging confirms occlusive thrombosis of the main portal vein. On endoscopy, grade 1 to 2 esophageal varices are noted and banded. Unfractionated heparin is begun. Subsequent workup reveals a homozygous factor V Leiden mutation. Long-term anticoagulation is planned, and she asks if warfarin can be avoided given her hectic ward rotations, erratic diet, and need for monitoring. Case 2: A 35-year-old woman who has no medical history seeks treatment for progressively worsening posterior headaches for 1 week. Magnetic resonance imaging of the brain shows dural sinus thrombosis with associated small areas of petechial cerebral hemorrhage. She is started on a continuous unfractionated heparin infusion and admitted to the hospital for further observation. Her grandmother is on warfarin for atrial fibrillation, and the patient would prefer to avoid warfarin because she does not think she can comply with the frequent monitoring that will be required. She inquires about other oral anticoagulant options for her condition.

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Fatal Dural Sinus Thrombosis Associated With Heterozygous Factor V Leiden and a Short Activated Partial Thromboplastin Time

Archives of Pathology & Laboratory Medicine ◽

10.5858/2003-127-1359-fdstaw ◽

2003 ◽

Vol 127 (10) ◽

pp. 1359-1361 ◽

Cited By ~ 2

Author(s):

Christina L. Stephan ◽

Karen SantaCruz ◽

Corrie May ◽

Steve B. Wilkinson ◽

Mark T. Cunningham

Keyword(s):

Partial Thromboplastin Time ◽

Primary Motor Cortex ◽

Sinus Thrombosis ◽

Factor V Leiden ◽

Activated Partial Thromboplastin Time ◽

Dural Sinus ◽

Factor V ◽

Dural Sinus Thrombosis ◽

Factor V Leiden Mutation ◽

Parietal Lobes

Abstract Inherited thrombophilia is a risk factor for dural sinus thrombosis (DST). To our knowledge, this is the first description with autopsy findings of a patient with DST associated with heterozygous factor V Leiden and a short activated partial thromboplastin time (aPTT). A 51-year-old woman presented with a 3-day history of headache, nausea, right-sided weakness, and focal motor seizure; she died 3 days after admission. At autopsy, a gross examination showed hemorrhage of bilateral parietal lobes and left primary motor cortex, uncal and tonsillar herniation, and pulmonary embolus of the right upper lobe. A microscopic examination of the brain showed an organizing thrombus in the superior sagittal sinus, diffuse cerebral edema, and extensive venous congestion. Laboratory studies showed heterozygous factor V Leiden by polymerase chain reaction and a very short aPTT of 17 seconds (reference range, 22–30 seconds). The combination of a heterozygous factor V Leiden mutation and a short aPTT may have contributed to the fatal DST in this patient.

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Postoperative dural sinus thrombosis in a patient in a hypercoagulable state

Journal of Neurosurgery ◽

10.3171/jns.2006.105.5.772 ◽

2006 ◽

Vol 105 (5) ◽

pp. 772-774 ◽

Cited By ~ 3

Author(s):

Bradley C. Lega ◽

Daniel Yoshor

Keyword(s):

Venous Thrombosis ◽

Sinus Thrombosis ◽

Anticoagulation Therapy ◽

Factor V Leiden ◽

Sufficient Evidence ◽

Controlled Study ◽

Dural Sinus ◽

Neurosurgical Procedures ◽

Factor V ◽

Factor V Leiden Mutation

✓ Spontaneous cerebral venous sinus thrombosis is a rare problem that may be encountered in patients with underlying thrombophilic disorders. It has also been reported as a postoperative complication following suboccipital, transpetrosal, and transcallosal approaches. The authors report on a 67-year-old man with two prior episodes of lower-extremity deep venous thrombosis who underwent transcallosal resection of a colloid cyst and in whom sagittal sinus thrombosis developed 2 weeks thereafter. Results of a subsequent hematological workup revealed both a factor V Leiden mutation and the presence of antiphospholipid antibodies, two thrombophilic risk factors that likely contributed to the development of delayed postoperative sinus thrombosis. Although the safety of low-molecular-weight heparin (LMWH) after craniotomy has not been established in a randomized, controlled study, there is sufficient evidence to justify its use for prophylactic anticoagulation therapy in patients at high risk for postoperative cerebral venous thrombosis. The authors propose using LMWH prophylaxis in patients with thrombophilic disorders who undergo neurosurgical procedures in proximity to dural sinuses in an effort to prevent catastrophic venous infarction.

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Management of a decompensated acute-on-chronic intracranial venous sinus thrombosis

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756286419895157 ◽

2019 ◽

Vol 12 ◽

pp. 175628641989515 ◽

Cited By ~ 2

Author(s):

Carmen Serna Candel ◽

Victoria Hellstern ◽

Tania Beitlich ◽

Marta Aguilar Pérez ◽

Hansjörg Bäzner ◽

...

Keyword(s):

Magnetic Resonance ◽

Endovascular Treatment ◽

Sinus Thrombosis ◽

Vasogenic Edema ◽

Factor V Leiden ◽

Venous Sinus ◽

Venous Stasis ◽

Left Frontal Lobe ◽

Factor V Leiden Mutation ◽

Venous Sinus Thrombosis

A 34-year-old female patient presented during the 10th week of her second gravidity with headache, nausea and vomiting 2 weeks before admission. Her medical history was remarkable for a heterozygous factor V Leiden mutation, elevated lipoprotein A, and a cerebral venous thrombosis (CVT) after oral contraceptive intake 15 years before. Magnetic resonance imaging (MRI) suggested acute and massive intracranial sinus thrombosis. Despite full-dose anticoagulation, the patient deteriorated clinically and eventually became comatose. Now, MRI/magnetic resonance angiography revealed vasogenic edema of both thalami, of the left frontal lobe, and of the head of the caudate nucleus, with venous stasis and frontal petechial hemorrhage. She was referred for endovascular treatment. Diagnostic angiography confirmed a complete superficial and deep venous sinus occlusion. Endovascular access to the straight and superior sagittal sinus was possible, but neither rheolysis nor balloon angioplasty resulted in recanalization of the venous sinuses. Monitored heparinization was continued and antiaggregation was initiated. The patient remained comatose for another 5 days and MRI showed progress of the cytotoxic edema. On day 6, infusion of eptifibatide at body-weight-adapted dosage was started. The following day, the patient improved and slowly regained consciousness. MRI confirmed regression of the edema. The eptifibatide infusion was continued for a total of 14 days. Thereafter two doses of 180 mg ticagrelor per os (PO) daily were started. The patient remained on acetylsalicylic acid (ASA), ticagrelor, and enoxaparin on an unchanged dosage regimen. She was discharged home 26 days after the endovascular treatment without serious neurological deficit, with the pregnancy intact. At the 30th week of pregnancy the dosage of ASA was reduced to 300 mg once PO daily. Cesarian delivery was carried out at the 38th week of pregnancy. The newborn was completely healthy. Ultima ratio therapeutic options for severe intracranial venous sinus thrombosis refractory to anticoagulation are discussed, with an emphasis on platelet-function inhibition.

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The Outcome of Pregnancy in Patients with Thrombophilia after Anticoagulation.

Blood ◽

10.1182/blood.v106.11.4164.4164 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4164-4164

Author(s):

Qingqi Jiang ◽

Judith Andersen

Keyword(s):

Unfractionated Heparin ◽

Fetal Loss ◽

Factor V Leiden ◽

Protein S ◽

Severe Bleeding ◽

Factor V ◽

Protein C Deficiency ◽

Factor V Leiden Mutation ◽

G20210a Mutation ◽

History Of

Abstract Background: Both inherited and acquired thrombophilia predispose pregnant women to venous thromboembolism and recurrent fetal loss. The safety profile and tolerability of low molecular heparin (LWMH) has allowed us to evaluate effects of anticoagulation in the outcome of pregnancy in patients with thrombophilia. Methods: 20 patients with thrombophilia received either tinzaparin or enoxaparin combined with aspirin before and during pregnancy and the outcome of pregnancy was monitored for a period of 2 years. The median age of the patients was 28 years (25–49); 75% were Caucasians, 20% were aferican-american, 5% were others. The inherited and acquired thrombophilias include Factor V leiden mutation, prothrombin mutation in G20210A, mutation in methylenetetrahydrofolate (MTHFR), protein S deficiency, protein C deficiency, hyperhomocyteinemia, antiphospholipid syndrome, sticky platelet syndrome, etc. The majority of patients had more than 2 thrombophilia factors and had history of miscarriage. 15 of 20 patients (75%) received tinzaparin and 4 of 20 (20%) patients received enxoparin subcutaneously before they were conceived. Only one patient received unfractionated heparin. The LWMH was continued during pregnancy until 34 to 36 weeks gestation when it was changed to unfractionated heparin in order to prevent large amount of bleeding from upcoming delivery. All of the patients also received aspirin prior, during, and after the pregnancy. There were 21 live births including one triplet and one twins. Only two patients were complicated with miscarriage. There was no episode of severe bleeding or thromboembolism during pregnancy or postpartum. Conclusion: LWMH and aspirin has been effective in the prevention of fetal loss in women with thrombophilia disorders.

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Clinical and laboratory characteristics of paediatric and adolescent index cases with venous thromboembolism and antithrombin deficiency

Thrombosis and Haemostasis ◽

10.1160/th14-02-0149 ◽

2014 ◽

Vol 112 (09) ◽

pp. 478-485 ◽

Cited By ~ 15

Author(s):

Verena Limperger ◽

Andre Franke ◽

Gili Kenet ◽

Susanne Holzhauer ◽

Ralf Junker ◽

...

Keyword(s):

Risk Factor ◽

Venous Thromboembolism ◽

Factor V Leiden ◽

High Risk Population ◽

Cerebral Veins ◽

Antithrombin Deficiency ◽

Factor V Leiden Mutation ◽

Paediatric Patients ◽

G20210a Mutation ◽

Index Cases

SummaryVenous thromboembolism [TE] is a multifactorial disease and antithrombin deficiency [ATD] constitutes a major risk factor. In the present study the prevalence of ATD and the clinical presentation at TE onset in a cohort of paediatric index cases are reported. In 319 un - selected paediatric patients (0.1–18 years) from 313 families, recruited between July 1996 and December 2013, a comprehensive thrombophilia screening was performed along with recording of anamnestic data. 21 of 319 paediatric patients (6.6%), corresponding to 16 of 313 families (5.1%), were AT-deficient with confirmed underlying AT gene mutations. Mean age at first TE onset was 14 years (range 0.1 to 17). Thrombotic locations were renal veins (n=2), cerebral veins (n=5), deep veins (DVT) of the leg (n=9), DVT & pulmonary embolism (n=4) and pelvic veins (n=1). ATD co-occurred with the factor- V-Leiden mutation in one and the prothrombin G20210A mutation in two children. In 57.2% of patients a concomitant risk factor for TE was identified, whereas 42.8% of patients developed TE spontaneously. A second TE event within primarily healthy siblings occurred in three of 313 families and a third event among siblings was observed in one family. In an unselected cohort of paediatric patients with symptomatic TE, the prevalence of ATD adjusted for family status was 5.1%. Given its clinical implication for patients and family members, thrombophilia testing should be performed and the benefit of medical or educational interventions should be evaluated in this high risk population.

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HELLP Syndrome and Cerebral Venous Sinus Thrombosis Associated with Factor V Leiden Mutation during Pregnancy

Case Reports in Obstetrics and Gynecology ◽

10.1155/2014/582890 ◽

2014 ◽

Vol 2014 ◽

pp. 1-3 ◽

Cited By ~ 1

Author(s):

Zeynep Ozcan Dag ◽

Yuksel Işik ◽

Yavuz Simsek ◽

Ozlem Banu Tulmac ◽

Demet Demiray

Keyword(s):

Hellp Syndrome ◽

Sinus Thrombosis ◽

Factor V Leiden ◽

Cerebral Venous Sinus Thrombosis ◽

Venous Sinus ◽

Factor V ◽

Hormonal Changes ◽

Factor V Leiden Mutation ◽

Venous Sinus Thrombosis ◽

Increased Risk

Preeclampsia is a leading cause of maternal mortality and morbidity worldwide. The neurological complications of preeclampsia and eclampsia are responsible for a major proportion of the morbidity and mortality for women and their infants alike. Hormonal changes during pregnancy and the puerperium carry an increased risk of venous thromboembolism including cerebral venous sinus thrombosis (CVST). Factor 5 leiden (FVL) is a procoagulant mutation associated primarily with venous thrombosis and pregnancy complications. We report a patient with FVL mutation who presented with CVST at 24th week of pregnancy and was diagnosed as HELLP syndrome at 34th week of pregnancy.

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CEREBRAL VEINS AND DURAL SINUS THROMBOSIS: A REVIEW OF 73 CASES

10.26226/morressier.5ab8f55dd462b8029238ca00 ◽

2018 ◽

Author(s):

Dragos Catalin Jianu

Keyword(s):

Sinus Thrombosis ◽

Dural Sinus ◽

Cerebral Veins ◽

Dural Sinus Thrombosis

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Intracranial Sinus Thrombosis in a Patient With Crohn Disease and Factor V Leiden Mutation

Archives of Pathology & Laboratory Medicine ◽

10.5858/2003-127-1037-istiap ◽

2003 ◽

Vol 127 (8) ◽

pp. 1037-1039 ◽

Cited By ~ 1

Author(s):

Jennifer Maag ◽

Richard A. Prayson

Keyword(s):

Inflammatory Bowel Disease ◽

Crohn Disease ◽

Bowel Disease ◽

Sinus Thrombosis ◽

Factor V Leiden ◽

Factor V ◽

Factor V Leiden Mutation ◽

Sagittal Sinus ◽

Venous Infarcts ◽

Inflammatory Bowel

Abstract There is a well-known risk of thrombosis in patients with inflammatory bowel disease. Documented cases of intracranial sinus thrombosis in this setting are rare. We present the case of a 30-year-old man with Crohn disease who spontaneously developed a superior sagittal sinus thrombosis and bifrontal infarcts that resulted in death. The patient was heterozygous for factor V Leiden mutation. The literature was searched to assess the frequency of cerebral venous infarcts in inflammatory bowel disease and the role that factor V Leiden plays in thrombosis in such patients.

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Arteriovenous Fistula After Cerebral Venous Sinus Thrombosis

Bangladesh Journal of Medicine ◽

10.3329/bjmed.v30i1.39921 ◽

2019 ◽

Vol 30 (1) ◽

pp. 35-37

Author(s):

Low Qin Jian ◽

Cheo Seng Wee

Keyword(s):

Magnetic Resonance ◽

Sinus Thrombosis ◽

Cerebral Venous Sinus Thrombosis ◽

Venous Sinus ◽

Dural Sinus ◽

Cerebral Vein ◽

Cerebral Veins ◽

Venous Infarction ◽

Venous Sinus Thrombosis ◽

Cortical Vein Thrombosis

Thrombosis of the deep cerebral vein is a rare entity. Thrombosis of cerebral veins or dural sinus obstructs blood drainage from brain tissue, leading to cerebral parenchymal dysfunction and increased venous and capillary pressure with disruption of the blood-brain barrier. Many conditions are associated with cerebral venous sinus thrombosis. Prothrombotic conditions, malignancy, infection and head injury has been reported as risk factors for cerebral venous sinus thrombosis (CVST). Neuroimaging features of CVST include focal areas of oedema or venous infarction, hemorrhagic venous infarction, diffuse brain edema or rarely subarachnoid haemorrhage. Magnetic resonance imaging of the brain in combination with magnetic resonance venography is the most informative technique in demonstrating the presence of dural thrombus and cortical vein thrombosis. Bangladesh J Medicine Jan 2019; 30(1) : 35-37

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