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.     

Antiphospholipid antibodies in children

Lupus anticoagulant (LA) is made up of heterogeneous IgG and IgM antibodies that prolong clotting times in vitro and is associated with an increased rate of both thrombosis and hemorrhage in vivo, although thrombosis is far more common. Many mechanisms of action have been explored, but none explains the coagulation abnormality of every sample tested. Binding of these antibodies to protein phospholipid complexes provides a unifying model. Antiphospholipid antibodies (APAs) are found in adult patients with a variety of disorders or as an isolated finding. The association of LA and anticardiolipin antibodies (ACAs) with thrombosis in adults has been established, although there is no test as yet to predict thrombotic risk for an asymptomatic affected individual. The presentation of thrombosis with postinfectious APA is uncommon in adults. Children who present with thrombosis and LA are found to have underlying disorders similar to those of adults. Although the presentation of thrombosis in children with postinfectious LA is rare, the association is established. LA-positive children with thrombosis have manifested a severe acquired deficiency of protein S; LA-positive children with hemorrhage have manifested an acquired deficiency of prothrombin. The association of thrombosis with ACA-positive children has been reported. Further work to determine the epidemiology, mechanism of action, and thrombotic potential of APA in children is warranted to better understand, prevent, and treat thrombotic and hemorrhagic complications.     

Co-segregation of thrombosis with the factor V Q506 mutation in an extended family with resistance to activated protein C

The activated protein C (APC) resistance phenotype results from a mutation at one of the cleavage sites of factor V by APC (Q506). We describe a large family with an APC resistance phenotype and without any other detectable coagulation defect, including eight subjects who had developed deep venous thrombosis (mean age of the first thrombosis episode 29 years; range 17-55 years). The factor V Q506 mutation was detected in the seven patients with thrombosis who could be tested and in 13 asymptomatic subjects (mean age 17 years; range 5-33 years). The APC resistance was detectable in only 10 heterozygotes among the 19 tested. These data suggest that, in affected families, the risk for the factor V Q506 mutation carriers to develop thrombosis may be very high and that factor V genotyping must be performed in patients with thrombosis even without any detectable APC resistance phenotype.     

Antiphospholipid antibodies in Turkish children with thrombosis.

Antiphospholipid syndrome is a systemic disorder characterized by arterial and/or venous thrombosis, thrombocytopenia, recurrent fetal loss, and presence of antiphospholipid antibodies (APA). The importance of APA in Turkish children with thrombosis is unknown. This study aimed to evaluate the frequency of APA positivity, associated risk factors other than APA, and outcome in children with APA and thrombosis. The presence of APA was investigated in 138 children presenting for evaluation of thrombosis; other prothrombotic risk factors were also studied. The frequency of APA positivity among 138 children was 11.6% (16/138). The mean age of these 16 children (10 female, 62.5%) was 9.57 +/- 4.59 years (range, 2.5-18.0 years). The mean follow-up period was 31.7 +/- 21.7 months (range, 5-60 months). Recurrence was observed during follow-up in two patients (12.5%). Ten patients (62.5%) had arterial thrombosis, five patients (31.3%) venous thrombosis, and one patient (6.3%) purpura fulminans. Among the thrombotic children with APA, 11 (68.8%) had more than one prothrombotic risk factor other than circulating APA [five patients (31.3%) had two risk factors, two patients (12.5%) had three, and four patients (25.0%) had four]. Five patients (31.3%) had no additional risk factors. APA should be tested in all children with thrombosis, especially those with arterial thrombosis.     

Activated protein C resistance and the factor V Leiden mutation in children with thrombosis

To determine the prevalence of activated protein C resistance and the factor V Leiden mutation (position 1691, arginine 506 to glutamine substitution) in children with thrombosis, plasma samples from children with thrombosis were tested for activated protein C resistance. DNA was analyzed for the factor V Leiden mutation. Five of 34 children (15%) had activated protein C resistance; each was heterozygous for the factor V Leiden mutation. All 5 children heterozygous for the factor V Leiden mutation suffered non-CNS venous thromboses comprising 21% of the group of children (5/24) with non-CNS venous thrombotic events. Each of these 5 children had a family history of thrombosis. In conclusion, children with non-CNS venous thrombosis should be evaluated for the factor V Leiden mutation. Children most likely affected are those with a family history of thrombosis. Am. J. Hematol. 57:29–32, 1998. © 1998 Wiley-Liss, Inc.     

The incidence of venous thromboembolism in asymptomatic carriers of a deficiency of antithrombin, protein C, or protein S: a prospective cohort study

Deficiencies of antithrombin, protein C, and protein S are associated with an increased risk of venous thromboembolism. The objective of this study was to prospectively assess the incidence of venous thromboembolism in nontreated asymptomatic subjects with such a deficiency. We conducted a prospective cohort study in asymptomatic family members of unselected patients who presented with a venous thromboembolic event and who were found to have a deficiency of antithrombin, protein C, or protein S. No anticoagulant prophylaxis was given to the study participants, except during risk periods for venous thromboembolism. All venous thromboembolic events were diagnosed by objective diagnostic tests. A total of 208 individuals with a mean age of 37 years (range, 15 to 79) were included in the study. A total of 611 patient observation years was obtained. Nine venous thromboembolic events occurred, resulting in an annual incidence of 1.5% (95% confidence interval [CI], 0.7 to 2.8) for the 3 deficiencies combined. Five of these events occurred spontaneously, resulting in an annual incidence of spontaneous venous thromboembolism of 0.8% (95% CI, 0.3 to 1.9). For antithrombin, protein C, and protein S deficiencies separately, this figure was 1.6%, 1.0%, and 0.4%, respectively. Thirty-four subjects experienced a total of 40 risk periods during which 4 venous thromboembolic events occurred (10% per risk period). We conclude that the use of continuous anticoagulant prophylaxis seems not warranted in asymptomatic individuals with a deficiency of antithrombin, protein C, or protein S. During risk periods for venous thromboembolism, adequate anticoagulant prophylaxis is necessary.     

Thrombophilia in childhood: to test or not to test

Inherited thrombophilia is defined as a genetically determined tendency to develop venous thromboembolism. In children, inherited thrombophilia contributes to the development of pediatric thromboembolic disease. As a consequence, pediatric hematologists are increasingly requested to test thrombophilia in pediatric patients with thrombosis or asymptomatic children from thrombophilic families. This article reviews the benefits and limitations of testing for thrombophilic disorders, for example, factor V Leiden, prothrombin mutation, and deficiencies of antithrombin, protein C, or protein S in childhood.     

Factor V Q 506 mutation in children with thrombosis

The factor V Leiden mutation in 12 children with thrombosis and in 20 controls was investigated. Five heterozygous individuals and 1 homozygous individual among the cases with thrombosis and 1 heterozygous individual among controls were found. Central nervous system thromboses were increased in children with the factor V mutation, associated with protein S deficiency. © 1996 Wiley-Liss, Inc.     

A young adult with coronary artery and jugular vein thrombosis: a case report of combined protein S and protein C deficiency

Protein C and protein S deficiencies increase the risk of thromboembolic events. We report a case of combined protein C and S deficiency in a young woman, with resulted in acute myocardial infarction and asymptomatic jugular vein thrombosis. The patient was treated successfully with coronary artery bypass graft surgery and systemic anticoagulation. Our report emphasizes that a combined deficiency of protein C and S may be a high risk factor for arterial thromboembolic events in young adults.     

Risk factors for thrombophilia in young adults presenting with thrombosis

The increased risk for thrombosis is known as hypercoagulability or thrombophilia. Here, we investigated risk factors for thrombophilia which were screened in young adult patients presenting with thrombotic events or with recurrent abortions with unknown etiology. A total of 115 patients aged between 16 and 50 years who were found to harbor thrombophilia were retrospectively evaluated. The laboratory investigations performed for the assessment of thrombophilia included protein C, protein S, antithrombin III deficiencies, activated protein C resistance, factor V Leiden (FVL), prothrombin 20210A (PT 20210) and methylenetetrahydrofolate reductase (MTHFR) gene mutations, factor VIII elevation, lupus anticoagulant and antiphospholipid antibodies (APA). In 66% of the cases a single thrombophilic defect was identified while some of the patients had combined thrombophilic defects. The most common thrombophilic defect was mutation in the MTHFR gene, and was followed by FVL mutation, the presence of APA and PT 20210 gene mutation, respectively. The patients were divided into two different age groups, 16–35 and 36–50 years, and arterial thrombosis was more common in the older age group. Our results indicated that some important thrombophilic defects such as gene mutations may appear in young adult patients presenting with thrombotic events.     

Prevalence of factor V Leiden mutation and other hereditary thrombophilic factors in Egyptian children with portal vein thrombosis: results of a single-center case-control study

No identifiable cause can be found in more than half of the cases of portal vein thrombosis (PVT). Our aim was to assess the prevalence of factor V Leiden mutation and other thrombophilic factors as risk factors in the development of PVT in the pediatric age group. From March 2001 to January 2002, 40 children with PVT were enrolled in the study, in addition to 20 age-matched and sex-matched controls. Protein C, protein S, antithrombin III, and activated protein C resistance (APCR) were assayed. Molecular study of factor II and factor V mutations was carried out. Of the patients, 25 had detectable hereditary thrombophilia (62.5%), 12 had factor V Leiden mutation (30%), 11 had protein C deficiency (27.5%), 6 had factor II mutation (15%), 1 had antithrombin III deficiency (2.5%), and none had protein S deficiency. Five children had concurrence of more than one defect. Factor V Leiden mutation is the most common hereditary thrombophilia associated with PVT and the relative risk of factor V Leiden mutation, as a cause of PVT, was six times more than in controls (odds ratio=6). Concurrence of more than one hereditary thrombophilic factor was seen in 12.5% of our patients. Circumstantial risk factors (neonatal sepsis, umbilical sepsis, umbilical catheterization) were not more significantly prevalent among patients with hereditary thrombophilia than among those with no detectable abnormalities in anticoagulation.An erratum to this article can be found at     

Cause of portal or hepatic venous thrombosis in adults: the role of multiple concurrent factors

According to a recent hypothesis, venous thrombosis results from the concurrence of several factors. This hypothesis was assessed in patients with portal or hepatic venous thrombosis by simultaneously investigating most of the currently identified prothrombotic disorders, local precipitating factors, and other risk factors such as oral contraceptive use. Patients with a tumorous obstruction and patients with cirrhosis with portal vein thrombosis were excluded. The prothrombotic disorders that were investigated included classical and occult myeloproliferative disorders; antiphospholipid syndrome; protein C; protein S and antithrombin deficiency; factor V Leiden; factor II; and methylene-tetrahydrofolate-reductase gene mutations. We found 1 or several prothrombotic disorders and a local precipitating factor in 26 and 10 of the 36 patients with portal vein thrombosis, respectively; and in 28 and none of the 32 patients with hepatic vein thrombosis, respectively. We found a combination of prothrombotic disorders in 5 and 9 patients with portal and hepatic vein thrombosis, respectively, whereas such a combination is expected in less than 1% of asymptomatic subjects. Of the 10 patients with a local precipitating factor, 8 had a prothrombotic disorder. Of the 13 patients who use oral contraceptives, 10 had a prothrombotic disorder. We conclude that portal or hepatic venous thrombosis should be regarded as an index for 1 or several prothrombotic disorders, whether or not local precipitating factors or oral contraceptive use are found. Concurrence of prothrombotic disorders is more common than expected. Extensive investigation of prothrombotic disorders and anticoagulation should be considered in patients with portal or hepatic venous thrombosis.     

Clinical and laboratory evaluation of Turkish children with thrombosis for homozygous factor V G1691A mutation.

Factor V (FV) G1691A mutation, in a heterozygous state, is one of the most common inherited risk factors for development of thrombosis. However, the clinical manifestations of homozygosity for the FV G1691A mutation in children is largely unknown because of the limited number of studies reported. The purpose of this study was to evaluate the clinical manifestations and laboratory findings of children with thrombosis who were homozygous for this mutation. Ten patients (four male/six female; mean age, 4.5 years; age range, 1-13 years) who were found to be homozygous for the FV G1691A mutation among 360 consecutive children with thrombosis (2.8%) were the subjects of this study. Six of the 10 patients had venous thrombosis, two had purpura fulminans, one had diffuse skin ecchymosis and one had arterial thrombosis. No history of thrombosis was present in their family members. Seven of the 10 children were under the age of 5 years. One or more additional risk factors (infection, protein S and protein C deficiencies, elevated factor VIII, etc.) were also present in nine of these patients. None of these patients had prothrombin G20210A mutation but one patient had risk-associated plasminogen activator inhibitor-1 gene 4G/4G genotype. These findings suggest that, in the presence of other underlying risk factors, homozygosity for FV G1691A mutation may lead to development of thrombosis at a very young age.     

Thromboembolism and resistance to activated protein C in patients with inflammatory bowel disease

OBJECTIVE: Thromboembolic events are serious complications in patients with inflammatory bowel disease (IBD). Resistance of factor V to degradation by activated protein C (APC) is a major cause for venous thrombosis and is found in approximately 30% of patients with thromboembolism. The aim of the present study was to assess the prevalence of APC resistance and clinical risk factors in patients with IBD. METHODS: One-hundred-two patients with IBD (64 women and 38 men; median age, 35 yr; range, 17-77 yr; 77 with Crohn's disease, 25 with ulcerative colitis) and 102 gender- and age-matched healthy control subjects were investigated prospectively for the presence of APC resistance. None of the healthy controls but 16 patients with IBD had a history of thromboembolism. RESULTS: Patients with IBD and thromboembolism were young, with a median age of 37 yr (range, 17-61 yr). Five (31.3%) of them had APC resistance, which was more common than in patients with IBD without thromboembolism (7%) and in controls (5.9%) (p < 0.01). Three patients had two thromboembolic events, the other 13 each had one. Deep vein thrombosis of the leg and pulmonary emboli were the most common thromboembolic complications (84.2%). Active disease, fistula, or bowel stenosis were found in 10 (52.6%) of 19 thromboembolic events; in three (15.8%) cases thromboembolism happened postoperatively. CONCLUSIONS: APC resistance is not associated with IBD but, when present, increases the risk of thromboembolism. Patients with IBD and thromboembolism are mostly young and clinical risk factors can be found in one-half of cases.     

Airway surface pH in subjects with cystic fibrosis.

The cystic fibrosis (CF) transmembrane conductance regulator protein can transport bicarbonate and may therefore regulate airway surface (AS) pH. Disturbances of AS pH could contribute to the pathophysiology of CF lung disease. Five studies were carried out including the following: study 1) nasal pH measurements were made in 25 CF and 10 non-CF adults using an antimony pH probe. Mean nasal pH was significantly lower in the CF group. Nasal potential difference may have been a confounding factor; study 2) in a fresh cohort of CF and non-CF subjects, no significant difference was found between the two groups using a gold pH probe; study 3) simultaneous nasal pH measurements were made in 15 CF and 15 non-CF adults using both probes. In the CF group, there was a trend for the antimony probe to read lower than the gold probe. In the non-CF group, the antimony probe read higher. The pH difference noted in study 1 related to technical factors; study 4) the effect of acute changes in serum acid/base balance on nasal pH was assessed in five non-CF adults. Nasal pH was not altered by either acute respiratory acidosis or alkalosis; study 5) nasal and lower airway pH was measured in five CF and six non-CF children. No difference was found between the groups. There was a correlation between nasal and lower airway pH. The authors conclude that airway surface pH does not differ between cystic fibrosis and noncystic fibrosis subjects and therefore, cystic fibrosis transmembrane conductance regulator may not play a major role in airway surface pH in vivo.     

No evidence for an increased risk of venous thrombosis in patients with factor V Leiden by the homozygous 677 C to T mutation in the methylenetetrahydrofolate-reductase gene.

Hyperhomocysteinemia is an established risk factor for arterial and venous thrombosis. Recently, it has been shown that a C to T mutation at nt position 677 in the methylenetetrahydrofolate-reductase (MTHFR) gene is a common cause of moderately elevated levels of plasma homocysteine in adults. In order to investigate whether the newly recognized genetic alteration in the MTHFR gene potentiates the thrombotic tendency in patients with factor V Leiden, we studied 81 unrelated patients with a history of venous thrombosis and a heterozygous factor V Leiden mutation. In addition, we analyzed 111 family members of 34 families in which the proband had a heterozygous factor V Leiden mutation. In all individuals, factor V Leiden and the MTHFR mutation were tested and the occurrence of venous thrombotic events was evaluated retrospectively. Seventy-seven healthy subjects without the factor V Leiden mutation or any other known thrombotic risk factor served as a control group. The prevalence of the homozygous MTHFR mutation was similar in index patients (10 of 81, 12%) and in the control group (10 of 77, 13%). The median age at first thrombosis in index patients was 32 years (range 22-69 years) in 10 patients with heterozygous factor V Leiden and T/T MTHFR mutation, and 34 years (range 6-72 years) in 71 patients with the factor V Leiden mutation only. In the family members, the prevalence of thrombosis was not higher in patients with factor V Leiden and +/+ MTHFR genotype than in those with only the heterozygous factor V Leiden mutation. We conclude from these data that the 677 C to T mutation in the MTHFR gene does not represent a significant additional risk factor for venous thrombosis in patients with factor V Leiden mutation.     

Lupus anticoagulant in children with thrombosis

Nineteen children who presented with thromboses over a 7-year period were found to have a lupus anticoagulant (LA). The initial thrombosis was proximal deep vein thrombosis (DVT) in six children, central nervous system (CNS) in five, primary pulmonary in four, distal DVT in two, central venous in one, and proximal arterial in one. Five children were diagnosed with systemic lupus erythematosus (SLE), including two children for whom thrombosis was the presenting sign of SLE. The remaining 14 children were diagnosed with the antiphospholipid antibody (APA) syndrome. The APA syndrome was manifest by venous or arterial thrombosis in association with a positive LA; positive anticardiolipin antibodies and a fine, speckled antinuclear antibody (ANA) pattern were additionally found in the majority of children. Approximately one-half of the children with SLE or the APA syndrome had a pulmonary embolus, and one-half developed recurrent thrombosis. Oral anticoagulation with coumadin to achieve an INR of >2.0 prevented thrombosis recurrence. The recognition of a LA in children with thrombosis necessitates evaluation for SLE, APA, and other autoantibodies. © 1995 Wiley-Liss, Inc.     

Anticoagulant proteins in childhood venous and arterial thrombosis: a review

Thrombotic disease is less frequent in children than in adults, but may result in severe morbidity and mortality. The coagulation system is balanced to provide rapid activation to stop bleeding and appropriate inhibition to prevent unwanted clot extension. It is regulated by fibrinolysis and by three major anticoagulant pathways: the protein C, antithrombin, and tissue factor pathway inhibitor systems. Acquired or inherited abnormalities of coagulation proteins or hemostatic regulatory mechanisms, particularly when combined with dehydration or the presence of indwelling catheters, may pose a high risk for thrombosis. Thrombosis in a child warrants investigation of potential underlying prothrombotic conditions. These include acquired antiphospholipid antibodies or the lupus anticoagulant as well as abnormalities of the inherited anticoagulant factors including protein C, protein S, antithrombin, and Factor V Leiden. Other abnormalities may result in heightened levels of otherwise normal coagulation proteins such as hyperprothrombinemia due to the prothrombin 20210 mutation. A large survey of children with thrombosis indicated that Factor V Leiden, protein C deficiency, and increased lipoprotein(a) were found most commonly. The most severe predisposition occurs with homozygous protein S or protein C deficiency with resultant purpura fulminans in the newborn. The risk of thrombosis in children with heterozygous deficiencies of anticoagulant proteins is not well defined, although it is clear that combined heterozygotes or a combination of an inherited and an acquired defect heightens the risk for thrombosis. Treatment of thrombosis primarily involves a rapidly acting anticoagulant such as heparin or low-molecular-weight heparin to prevent extension, and long-term anticoagulation with warfarin may be instituted to prevent recurrence. Fibrinolytic therapy is infrequently used because of the risk of serious bleeding complications and is reserved for selected cases of arterial thrombosis to initiate rapid reperfusion of ischemic tissue or used in those patients with a large venous thrombosis and pulmonary emboli causing hemodynamic compromise.     

Evaluation of thrombotic children with malignancy

The purpose of this study was to evaluate inherited and acquired prothrombotic risk factors among children with malignancies who have thrombosis and emphasize the importance of inherited prothrombotic risk factors. Thirty-seven consecutive children with thrombosis and malignancy were included in this study. The patients were evaluated separately for time of development of thrombosis, insertion of a central venous line (CVL), history of l-asparaginase usage, and recent infections. Prothrombotic risk factors such as factor V G1691A and prothrombin G20210A mutation, protein C, protein S, antithrombin III deficiencies, factor VIII and lipoprotein(a) elevation, and antiphospholipid antibodies were analyzed for all patients. Of 387 children with thrombosis, 37 (9.5%) had a malignancy. Thrombosis was detected in 9 patients at the time of diagnosis, during maintenance therapy in 25 patients, and after the discontinuation of treatment in 3 patients. One or two additional prothrombotic risk factors other than l-asparaginase therapy and insertion of central venous lines were present in 20 of these patients (54%). It was found that eight patients had the factor V G1691A mutation in the heterozygote state. One of them had the factor V G1691A mutation associated with a history of infection and one patient had the factor V G1691A mutation associated with factor VIII elevation. One had the the prothrombin G20210A mutation in the heterozygote state, four had lipoprotein(a) elevation, two had factor VIII elevation, one had a decreased protein S level, one had a decreased protein C level, one had antiphospholipid positivity, and two had histories of infection. Malignancy is an important risk factor for the development of childhood thrombosis. However, the risk of thrombosis increases when accompanied by additional prothrombotic risk factors. For this reason, especially children with malignancy and at high risk for the development of thrombosis, such as those who have received l-asparaginase or a replaced CVL during their therapy, might be screened for additional prothrombotic risk factors and appropriate measures might be taken to prevent the development of thrombosis.     

Prevalence of inherited prothrombotic abnormalities and central venous catheter-related thrombosis in haematopoietic stem cell transplants recipients

In this prospective study, we assessed the incidence of central venous catheter (CVC)-related thrombosis in haematopoietic stem cell transplant (HSCT) recipients. We determined the contribution of inherited prothrombotic abnormalities in blood coagulation to CVC-related thrombosis in these patients. The study was conducted between May 2002 and September 2004. CVCs were externalized, nontunneled, polyurethane double lumen catheters. Before catheter insertion, laboratory prothrombotic markers included factor V Leiden, the prothrombin gene Gly20210A mutation, plasma antithrombin levels, and protein C and S activity. All patients were systematically examined by ultrasonography just before, or <24 h after, catheter removal, and in case of clinical signs of thrombosis. A total of 171 patients were included during the 28-month study period. Five (2.9%) and three (1.7%) patients had evidence of protein C and protein S deficiency, respectively. Only one patient had an antithrombin deficiency (0.6%). In total, 10 patients (5.8%) were heterozygous for the factor V Leiden mutation, and one patient had heterozygous prothrombin G20210A mutation (0.6%). We observed a CVC-related thrombosis in 13 patients (7.6%). Thrombosis was diagnosed in four out of 20 patients (20%) with a inherited prothrombotic abnormality compared to nine of 151 patients (6%) who did not have a thrombophilic marker (relative risk 3.3 CI 95% 1.1-9.9). Our results suggest that inherited prothrombotic abnormalities contribute substantially to CVC-related thrombosis in HSCT recipients. In view of physicians' reluctance to prescribe prophylactic anticoagulant treatment in these patients, a priori determination of inherited prothrombotic abnormalities may form a basis to guide these treatment decisions.