Evidence Of Thrombophilia Research Articles

Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination

BackgroundThe mainstay of control of the coronavirus disease 2019 (Covid-19) pandemic is vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Within a year, several vaccines have been developed and millions of doses delivered. Reporting of adverse events is a critical postmarketing activity.MethodsWe report findings in 23 patients who presented with thrombosis and thrombocytopenia 6 to 24 days after receiving the first dose of the ChAdOx1 nCoV-19 vaccine (AstraZeneca). On the basis of their clinical and laboratory features, we identify a novel underlying mechanism and address the therapeutic implications.ResultsIn the absence of previous prothrombotic medical conditions, 22 patients presented with acute thrombocytopenia and thrombosis, primarily cerebral venous thrombosis, and 1 patient presented with isolated thrombocytopenia and a hemorrhagic phenotype. All the patients had low or normal fibrinogen levels and elevated d-dimer levels at presentation. No evidence of thrombophilia or causative precipitants was identified. Testing for antibodies to platelet factor 4 (PF4) was positive in 22 patients (with 1 equivocal result) and negative in 1 patient. On the basis of the pathophysiological features observed in these patients, we recommend that treatment with platelet transfusions be avoided because of the risk of progression in thrombotic symptoms and that the administration of a nonheparin anticoagulant agent and intravenous immune globulin be considered for the first occurrence of these symptoms.ConclusionsVaccination against SARS-CoV-2 remains critical for control of the Covid-19 pandemic. A pathogenic PF4-dependent syndrome, unrelated to the use of heparin therapy, can occur after the administration of the ChAdOx1 nCoV-19 vaccine. Rapid identification of this rare syndrome is important because of the therapeutic implications.

Endovascular treatment of an obstructive membrane between inferior vena cava and right atrium in an unrecognized Budd-Chiari syndrome

BackgroundBudd-Chiari syndrome is defined as a hepatic venous outflow track obstruction of various etiology, which appears at different levels. The inferior vena cava outflow membrane is an unusual, but a potentially treatable cause. The percutaneous treatment has emerged as a very promising management mode for such patients. Follow-up results are favorable for balloon angioplasty and/or stenting, with minimal re-stenosis rates.Case presentationWe report a case of a young woman, earlier operated on congenital heart defect and with previous pulmonary embolic incident after childbirth, with no evidence of thrombophilia. She was admitted to our institution for a suspected right atrial tumor. After the diagnosis of Budd-Chiari syndrome caused by membranous inferior vena cava obstruction, a percutaneous treatment of a thick membrane was successfully performed, using an unusual technique.ConclusionBalloon angioplasty should be considered in cases of membranous obstruction of vena cava, where a focal obstruction is causing the symptoms. In our patient, the anatomy was not suitable for stenting, and balloon dilatation was successful just after the membrane was pulled apart with a big balloon in a “Rashkind-like” procedure.

Finger necrosis with eosinophilia and symmetrical occlusion of the peripheral artery

Case presentationA 59-year-old man with hypertension, dyslipidemia and a current smoking history had presented with bilateral painful finger ulcers (figure 1A). The patient was referred to our hospital for the...

The Prevalence of Thrombophilia in Women With Recurrent Fetal Loss and Outcome of Anticoagulation Therapy for the Prevention of Miscarriages

To estimate the prevalence of thrombophilia in women with recurrent miscarriages and to assess the effect of antithrombotic therapy. A retrospective cohort study between the years 2004 and 2010. A hypercoagulation community clinic in northern Israel. Four hundred ninety pregnant women referred for thrombophilia screening. Screening results for thrombophilia and antithrombotic treatment with enoxaparin, aspirin, or both and pregnancy outcomes. The most common thrombophilia in our study group was factor V Leiden mutation with a prevalence of 20.9% followed by protein S deficiency with a prevalence of 19%. Live birth rate was higher in the group of women who received enoxaparin regardless of whether a specific thrombophilia could be found. This finding was more pronounced in women who had ≥4 miscarriages. The prevalence of thrombophilia was higher in our study group than in the general population. Furthermore, treatment with enoxaparin might improve the rate of live births in women with or without evidence of thrombophilia, especially in women with ≥4 miscarriages.

PP04.10 – 2544: Trichothiodystrophy presenting with cardiomyopathy and recurrent arterial ischemic strokes

Objective Considerable differences exist between arterial ischemic stroke (AIS) in childhood and adults. Among others, a wider spectrum of rare etiologies has to be considered in children. Trichothiodystrophy (TTD) is a rare genetic syndrome characterized by typical hair texture, variable photosensitivity, xerosis cutis, short stature and psychomotor retardation. We report a child with TTD and recurrent AIS. Methods Case report. Results A 3-year-old boy presented with acute onset of left hemiparesis and facial nerve palsy. Brain magnetic resonance imaging (MRI) revealed an extensive acute ischemic infarction involving the right middle cerebral artery (MCA) territory with sparing of the basal ganglia. Intravenous thrombolysis with tPA within 3 hours after onset led to recanalisation and dramatic clinical improvement. Aspirin treatment was initiated for secondary stroke prevention. However, on day 7 a focal epileptic seizure occurred. MRI showed acute DWI/ADC positive lesions in the left MCA territory. Intravenous thrombolysis was administered again, however, without success. Two days later he suffered from reinfarction involving his right MCA and left posterior cerebral artery. There was no evidence of thrombophilia, dyslipidaemia, sickle cell disease, metabolic or autoimmune disease. His past medical history was relevant for developmental delay and dilated cardiomyopathy of unknown origin. A dilated left ventricle but no thrombi could be detected with echocardiography. Since birth he had been suffering from dry, scaly skin. A striking hair texture with brittle, short hair with patchy thinning and alopecic areas was found. Electron and polarization microscopy confirmed TTD. Conclusion This is the second documented case of AIS associated with TTD (Toelle et al., 2001). Uncommon hair structure in combination with cardiomyopathy and stroke should lead to investigations for TTD. Although AIS secondary to cardiac embolism has been suggested, the aggressive course in our patient led us to speculate that additional factors inherent in TTD might have contributed.

High prevalence of protein C, protein S, antithrombin deficiency, and Factor V Leiden mutation as a cause of hereditary thrombophilia in patients of venous thromboembolism and cerebrovascular accident.

Objectives: To determine the frequency of Protein C, Protein S (PC & PS), antithrombin deficiency (AT III) and Factor V Leiden mutation (FVL) as a cause of thrombophilia in the patients with venous thromboembolism (VTE) and cerebrovascular accident (CVA). Methods: It was an observational study conducted at Department of Haematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan. All patients referred for thrombophilia screening from July 2009 to June 2012 were screened. Patients with evidence of VTE or CVA were screened for PC & PS, AT III deficiency, and FVL. Results: Total 404 patients of age between 1-71 years mean 33 ± 14 with male to female ratio of 2.4:1 had evidence of thrombophilia. Two hundred eighteen (54%) patients presented with CVA, 116 (29%) with deep vein thrombosis (DVT), 42 (10.5%) with pulmonary embolism (PE), and 28 (7.5%) with portal or mesenteric vein thrombosis (PV). Protein C & S deficiency was detected in 35/404 (8.7%), ATIII in 9/404 (2%), and FVL in 25/173 patients (14.5%). The findings were suggestive of a significant association of FVL mutation for developing DVT (OR=11.0, 95% C I 4.6-26.3), CVA (OR=5.7, 95% C I 2.1-15.1), and PV (OR=5.4, 95% C I 1.3-21.9). PC & PS deficiency was a significant risk factor for developing PE (OR=3, 95% C I 0.8-11.4). Conclusion: FVL mutation and Protein C & S are the leading causes of thrombophilia with strong association of Factor V Leiden mutation as risk for developing DVT.

Question From the Clinician: Risk of Thrombophilia

A 17-year-old girl meets with you to discuss her use of oral contraceptives (OCPs) that contain estrogen. In the family history focusing on evidence of thrombophilia, you find that the patient’s father died of a pulmonary embolus after disembarking from a transatlantic airplane flight. The patient and her mother want to know if she should use OCPs. The girl is leaving for college, and there is concern for an unwanted pregnancy on the one hand and the risk of thrombosis on the other. How should you advise her?In this case, the family history provides a vital piece of information in assessing risk of thrombosis for this patient using OCPs. The current guidelines of the American College of Obstetrics and Gynecology do not recommend laboratory testing for thrombophilia if a careful family history is unrevealing. (1) In view of the father’s pulmonary embolus and demise, a consideration of inherited abnormalities that may predispose to a thrombus and acquired conditions that may provoke a thrombus is warranted. The father’s long airplane ride, particularly if it was in the coach section with limited mobility, is a risk factor for a lower extremity or pelvic thrombus and consequent pulmonary embolus, although at least one-third to one-half of the adult patients who experience pulmonary emboli do not have an identifiable source of the embolization. (2) The thrombotic risk would be heightened if he had an underlying malignancy or inflammatory disease, but there was no history of either of these conditions.If the immobilization of the airplane ride were coupled with an inherited thrombophilic condition, such as factor V Leiden (5% of the population), the risk would be more than additive. In the scenario presented, we have no information about an underlying thrombophilic mutation; but the population frequency of such abnormalities makes it reasonable to explore this possibility in this young woman in view of her positive family history, because such a mutation would increase her risk of a thrombus if she used OCPs.An established thrombophilia panel includes genetic and plasma-based testing, (3)(4)(5) as follows:The results of plasma-derived coagulation tests performed in children should be compared with their respective age-appropriate values. (6) Furthermore, each thrombophilic factor noted presents a different risk for the development of a thrombus. (7)The routine testing of children for both acquired and inherited conditions is controversial, given the low prevalence of thrombotic events, the even lower prevalence of unprovoked events, and the variable presence of external risk factors (eg, limited mobility, central lines, estrogen-containing OCP medications). Thrombophilia testing to determine the duration of anticoagulation in children or to prevent venous thromboembolism or life-threatening events in adolescent patients being considered for oral contraception has not been recommended in the absence of a family or patient history of thrombosis. (8)(9)The patient in the case described should have a complete evaluation for a thrombophilic factor. If a risk factor is identified, estrogen-containing OCPs should not be used. If an abnormality is detected, it would be beneficial to take a multidisciplinary approach, involving a pediatric hematologist and a gynecologist, to consider the different contraceptive methods that are compatible with the results of the thrombophilia investigation. (10) Current data do not indicate any heightened risk of thrombosis with the use of progesterone alone as a contraceptive, and numerous barrier methods of contraception are available. Importantly, additional modifiable risk factors such as obesity, inappropriate diet and sedentarism, and exposure to alcohol and tobacco also need to be addressed.

Factor V Leiden and Antiphospholipid Antibodies in Either Mothers or Infants Increase the Risk for Perinatal Arterial Ischemic Stroke

The objective was to investigate the role of infant and maternal thrombophilia in a cohort of mothers and infants presenting with perinatal arterial ischemic stroke. Forty-seven infants with clinically and radiologically confirmed perinatal arterial ischemic stroke underwent thrombophilia workup: factor V Leiden (FVL), PII20210A mutation, Methylene-tetrahydrofolate reductase 677T polymorphism, protein C, protein S, antithrombin, FVIII, and antiphospholipid antibodies. Thrombophilia data were available for 23 mother-infant pairs and compared with control populations to evaluate the risk for PAS. Thirty of 47 (64%) infants and 15 of 22 mothers (68%) had evidence of thrombophilia. In 18 of 23 (78%) mother-infant pairs, there was at least 1 thrombophilic risk factor, but 15 pairs were mismatched in pathology. Among infants, FVL, protein C deficiency, and presence of antiphospholipid antibodies prevailed (OR, 4.2; 95% CI, 1.5-11.3; OR, 12.2; 95% CI, 2.5-59.9; OR, 4.1; 95% CI, 1.4-12.2, respectively). Interestingly FVL prevailed in almost one-third of mothers (OR, 8.5; 95% CI, 4.1-17.5) and 18% of mothers had antiphospholipid antibodies (OR, 3.8l; 95% CI, 1.5-10.0). Maternal and neonatal thrombophilia, especially presence of FVL or antiphospholipid antibodies, may be important in the pathogenesis of perinatal arterial ischemic stroke. The nature of thrombophilic mother-infant risk potential interactions warrants further investigation.

Risk of Pregnancy-Associated Venous Thromboembolism in Women with a History of Prior Thrombosis.

Background: Previous estimates of the rate of recurrent venous thromboembolism (VTE) during pregnancy in women with a history of VTE have vary between 0 and 13%. Therefore, the decision to administer or withhold heparin - especially in the antepartum period - has been discussed controversial. In a recent study by Brill-Edwards et al. ( N Engl J Med 2000; 343:1439–44), no recurrences of VTE occurred in women (n=44) who had a previous episode of thrombosis that was associated with a temporary risk factor and who also had no evidence of thrombophilia. Based on these results, antepartum heparin prophylaxis is not routinely recommended in women without thrombophilia whose previous episode of thrombosis was associated with a temporary risk factor (ACCP guidelines 2004). The objective of our study was to evaluate the risk of recurrent pregnancy-associated thrombosis in women with a history of VTE.Materials and Methods: We retrospectively studied 198 women with at least one pregnancy (275 pregnancies in total) after a one previous episode of VTE. Sixty-three women (81 pregnancies) were excluded from the analysis because of antepartum heparin prophylaxis.Results: In the subgroup of women without heparin prophylaxis (n=135), 15 (7.7%) thromboembolic events occurred antepartum in 194 pregnancies. Further subgroup analysis, stratified for the nature of first VTE, gave the following number of antepartum VTE per number of pregnancies: 2 VTE/19 pregnancies (10.5%) in 14 women (first VTE: immobilization), 4 VTE/33 pregnancies (12.1%) in 24 women (first VTE: surgery), 5 VTE/69 pregnancies (7.2%) in 46 women (first VTE: oral contraception), 2 VTE/58 pregnancies (3.4%) in 40 women (first VTE: pregnancy), 2 VTE/15 pregnancies (13%) in 11 women (first VTE: idiopathic). Nine of the 15 women with VTE (7/13 women with first VTE triggered by temporary risk factor; 2/2 women with first idiopathic VTE) had a heterozygous factor V Leiden G1691A or prothrombin G20210A gene mutation. In the postpartum period, 16 VTE in 194 pregnancies occurred after live birth in the 135 women without heparin prophylaxis. Nine of these 16 women had a heterozygous FVL or prothrombin G20210A gene mutation. In Conclusion, the risk of recurrent antepartum VTE was similar in women with and without factor V Leiden G1691A or the prothrombin G20210A gene mutation and did not differ between women with first VTE triggered by a transient risk factor or an idiopathic first VTE. In addition to recommended postpartum heparin prophylaxis, our data support the need for a routine antepartum prophylaxis in women without thrombophilia whose previous episode of thrombosis was associated with a temporary risk factor.

The prevalence of thrombophilia in patients with symptomatic peripheral vascular disease

The aim of this prospective study was to establish the prevalence of thrombophilia and hyperhomocysteinaemia using a comprehensive screen in patients with peripheral vascular disease. A total of 150 patients with peripheral vascular disease (with an ankle brachial pressure index of less than 0.8) underwent thrombophilia screening (protein C and protein S, antithrombin, lupus anticoagulant, activated protein C resistance and factor V Leiden and prothrombin mutations). Fasting homocysteine assays were also performed. A thrombophilia defect was found in 41 patients (27.3 per cent). The commonest was protein S deficiency, found in 17 patients (11.3 per cent). Others included factor V Leiden mutation, found in 10 (6.7 per cent) and protein C deficiency, found in six (4.0 per cent). Lupus anticoagulant and prothrombin mutation were both found in six (4.0 per cent). One patient had an antithrombin deficiency. Only the presence of critical ischaemia was associated with a positive thrombophilia screen on single variable analysis (P = 0.03). Hyperhomocysteinaemia was present in over a third of the study group (37.3 per cent): 45 defined as moderate and 11 as intermediate. A quarter of patients with peripheral vascular disease had evidence of thrombophilia, and a third had hyperhomocysteinaemia.

Thrombophilia in children with cystic fibrosis

In some children with cystic fibrosis (CF), percutaneous long lines occlude sooner than expected (due to thrombophlebitis or thrombosis), and many have a totally implantable venous access device (TIVAD), a recognized complication of which is thrombosis. This complication is more likely if the child has an underlying thrombotic tendency, which may be enhanced in the presence of inflammatory lung disease. There are no reports of an identified association of heritable thrombophilia with CF, although individual cases have been recognized. Our aim was to determine the incidence of thrombophilia in children with CF. In a tertiary pediatric CF center, blood was screened for thrombophilia at annual review, and retested if abnormal. A thrombotic abnormality was found in 41/204 (20%) patients. These included activated protein C resistance (10/204, 5%) with a prevalence similar to that expected, but the following abnormalities had an increased prevalence: antithrombin deficiency (2/204, 1%), protein S deficiency (11/204, 5%), protein C deficiency (8/204, 4%), and lupus anticoagulant (18/204, 9%). There were no differences found in those with thrombophilia for the following parameters: age, gender, genotype, lung function, presence of Pseudomonas aeruginosa, prothrombin time, serum IgE, aspergillus-specific IgE, liver function, and blood inflammatory markers. Fifteen children had TIVADs, 4 of whom had evidence of thrombophilia. In conclusion, a significant proportion of patients had a thrombophilic abnormality. We recommend that thrombophilia screening be performed prior to insertion of a TIVAD, and also in those with a history of venous thrombosis, blocked TIVADs, or recurring problems with long lines.

Management of Thrombophilia in Renal Transplant Patients

Renal allograft recipients with thrombophilia (a hypercoagulable state) are at higher risk for early allograft loss. Following an episode of allograft renal vein thrombosis in a patient subsequently diagnosed with protein C deficiency, we adopted universal screening for hypercoagulable risk factors. Patients with a history of a thromboembolic event underwent laboratory screening for thrombophilia. Eight patients with a defined hypercoagulable disorder or a strong clinical history of thrombosis even in the absence of hematologic abnormalities were treated with anticoagulation following renal transplantation. We reviewed the outcomes of these eight patients and all renal transplant recipients at our center who developed thrombotic complications after renal transplantation. Since the introduction of universal screening for hypercoagulable risk factors, 235 consecutive transplants were performed without allograft thrombosis. Eight patients with evidence of thrombophilia, recognized before renal transplantation, received perioperative heparin and postoperative oral anticoagulation. Two of these eight patients developed perinephric hematomas requiring evacuation, blood transfusion, and temporary withholding of anticoagulation. Of interest, two of the remaining 227 patients, not identified with thrombophilia before surgery, developed thrombotic complications after renal transplantation. A hypercoagulable disorder was subsequently documented in each. Identifying patients with thrombophilia before transplantation and defining their management presents many challenges. The risk of allograft thrombosis must be weighed against the risk of perioperative bleeding and the need for long-term anticoagulation. Recommendations for managing thrombophilia in renal transplant recipients are suggested based on our experience and review of the literature.

Safety of Withholding Heparin in Pregnant Women With a History of Venous Thromboembolism

Background Women with a history of venous thromboembolism may be at increased risk for venous thromboembolic events during pregnancy. In these women, the decision to give or withhold heparin in the antepartum period is controversial, because accurate estimates of the frequency of recurrent thromboembolic events if antepartum heparin is withheld are not available. Methods We prospectively studied 125 pregnant women with a single previous episode of venous thromboembolism. Antepartum heparin was withheld, but anticoagulant therapy was given for four to six weeks post partum. Our primary objective was to determine the rate of antepartum recurrence of venous thromboembolism. Laboratory studies were performed to identify thrombophilia in 95 women. Results Three of the 125 women (2.4 percent) had an antepartum recurrence of venous thromboembolism (95 percent confidence interval, 0.2 to 6.9 percent). There were no recurrences in the 44 women who had no evidence of thrombophilia and who also had a previous episod...

Thrombose veineuse profonde contemporaine d'une varicelle de l'adulte

Some viral infections are associated with deep venous thrombosis. We report a case of deep venous thrombosis in an adult with varicella. He had neither known predisposing factors for thrombosis nor thrombophilia. Transient significant level of antiphospholipid antibodies and lupus circulating anticoagulant were observed. There was no evidence of thrombophilia. Deep venous thrombosis has been mostly associated with varicella in children. A transient protein S deficiency was present in almost all cases, though it was sometimes related to an anti-protein S antibody. This association is exceptional in adults. Some viruses such as herpesvirus and HIV are responsible for endothelium dysfunction, but this is still unclear in the case of varicella-zoster virus. In our observation, endothelium activation or antiphospholipid antibodies might be responsible for thrombosis.