The Spectrum of Hypercoagulable States in Minority Patients with Unexplained Thrombosis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4111-4111
Author(s):  
Damanjit K. Ghuman ◽  
Alice J. Cohen
Keyword(s):  
Protein C ◽  
Antithrombin Iii ◽  
Protein S ◽  
Minority Populations ◽  
Antiphospholipid Antibody ◽  
Protein S Deficiency ◽  
White Population ◽  
S Deficiency ◽  
Prothrombin Gene Mutation ◽  
Prothrombin Gene

Abstract The association of genetic risk factors with hypercoagulable states in minority populations has not been well defined. With an estimated prevalence of anywhere between 2-15% in healthy individuals, activated protein C resistance (APCR/Factor V Leiden) is considered to be the most common risk factor for venous thromboembolism( VTE) in the white population. It has also been postulated that this mutation is extremely rare in non-white populations. The prevalence of the prothrombin gene mutation G20210A in the white population is estimated at 0.7–4%, protein C and S deficiencies at 2% each and antithrombin III deficiency at 0.1–0.5% but unknown in Blacks with VTE though case control studies have identified protein C and protein S deficiencies in this population. This study is a retrospective review of all patients with thrombophilia registered at the Hemophilia Treatment Center between 1999–2005. 45/164(27%) of patients with thrombophilia were identified to be from minority groups. Of these minority patients 23/45(51%) had an identifiable primary hypercoagulable state. This group included 7/23(30%) males and 16/23(70%) females. The mean age of the patients was 35 years (range 12–80 years ). 4/23( 17%) were smokers and only 4/23(17%) had a family history of thrombosis with no documented hypercoagulable states in any family members. The majority of the patients were of African American descent 16/23(69%), 5/23(22%) were Hispanic and 2/23(9%) were Asians. 16/23(69%) of the patients had documented deep venous thrombosis/pulmonary embolus, 1/23(4%) had arterial thrombosis, 3/23(13%) had fetal loss, and 2/23(9%) were asymptomatic. APCR was the most common diagnosis in 8/23(35%) of the patients, followed by antiphospholipid antibody syndrome in 7/23(30%) of the patients. Protein S deficiency was diagnosed in 5/23(22%), hyperhomocysteinemia in 4/23(17%), Protein C deficiency in 1/23(4%), antithrombin III in 1/23(4%), and prothrombin gene mutation in 1/23(4%) of the patients. 4/23(17%) of the patients were found to have two coexisting hypercoagulable diagnoses. Recurrent VTE occurred in 7/23(30%) of the patients. Conclusion: Primary hypercoagulable states are not rare in minorities. In this study, APCR was found to be the most common identified abnormality, followed by antiphospholipid antibody and protein S deficiency. Similar to the white population, thrombophilia in minorities occurred more commonly in young female patients. Work up for primary hypercoagulable states should be considered in minority patients with unexplained thrombosis. Further studies are warranted to determine the true prevalence of hypercoagulable states in minority populations.

The Frequency of Type I Heterozygous Protein S and Protein C Deficiency in 141 Unrelated Young Patients with Venous Thrombosis

1988 ◽  
Vol 59 (01) ◽  
pp. 018-022 ◽  
Author(s):  
C L Gladson ◽  
I Scharrer ◽  
V Hach ◽  
K H Beck ◽  
J H Griffin
Keyword(s):  
Venous Thrombosis ◽  
Protein C ◽  
Antithrombin Iii ◽  
Young Patients ◽  
Protein S ◽  
Type I ◽  
Protein S Deficiency ◽  
Protein C Deficiency ◽  
Low Protein ◽  
S Deficiency

SummaryThe frequency of heterozygous protein C and protein S deficiency, detected by measuring total plasma antigen, in a group (n = 141) of young unrelated patients (<45 years old) with venous thrombotic disease was studied and compared to that of antithrombin III, fibrinogen, and plasminogen deficiencies. Among 91 patients not receiving oral anticoagulants, six had low protein S antigen levels and one had a low protein C antigen level. Among 50 patients receiving oral anticoagulant therapy, abnormally low ratios of protein S or C to other vitamin K-dependent factors were presented by one patient for protein S and five for protein C. Thus, heterozygous Type I protein S deficiency appeared in seven of 141 patients (5%) and heterozygous Type I protein C deficiency in six of 141 patients (4%). Eleven of thirteen deficient patients had recurrent venous thrombosis. In this group of 141 patients, 1% had an identifiable fibrinogen abnormality, 2% a plasminogen abnormality, and 3% an antithrombin III deficiency. Thus, among the known plasma protein deficiencies associated with venous thrombosis, protein S and protein C. deficiencies (9%) emerge as the leading identifiable associated abnormalities.

Retrospective Review of Hypercoagulability in Minority Populations at an Inner City Hospital’s General Hematology Clinic.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3973-3973
Author(s):  
Pritesh R. Patel ◽  
Manila Gaddh ◽  
Sunita Nathan ◽  
Griza Decebal ◽  
Rosalind Catchatourian ◽  
...  
Keyword(s):  
African American ◽  
Inner City ◽  
Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Minority Populations ◽  
Factor V ◽  
History Of ◽  
Prothrombin Gene Mutation ◽  
Prothrombin Gene

Abstract Background: Although much is known about the incidence of hypercoagulable disorders in the Caucasian population, data is lacking in many other racial groups. We therefore retrospectively analyzed charts of all patients referred to our inner city hospital’s general hematology clinic from January 2003 to December 2006 for evaluation of possible hypercoagulable state. Methods: We reviewed charts for all patients referred for investigation of thrombophilia or hypercoagulable state seen in our clinic. Data regarding history of thrombosis was recorded. In the case of venous thromboembolic disease possible precipitants were noted. Demographic data and family history were noted. A clinical diagnosis of hypercoagulability was made based on whether the patient had any of the following: age <40; strong family history of thrombosis; unusual location of thrombosis; 2 or more thrombotic events; lack of precipitant to thrombotic episode. Laboratory data was gathered on the following: factor V leiden mutation; prothrombin gene mutation; MTHFR mutation; antithrombin III levels; protein C and protein S function; antiphospholipid antibodies. Results: 59 patients were referred. Of these 12 patients were excluded from further analysis as the reason for referral was investigation of ischemic stroke or myocardial infarction. Using the above clinical criteria 33 patients were identified as having hypercoagulability. Diagnoses and demographics are noted in tables 1 and 2. Conclusions: Our study illustrates several important practical points about the investigation of hypercoagulable patients. A larger number of protein C or S deficiencies would likely have been diagnosed had these studies been performed prior to starting anticoagulation. Similarly it is likely that the proportion of patients diagnosed with antiphospholipid antibody syndrome is high as it is possible to test for this condition whilst patients are anticoagulated. It is therefore appropriate that the best time for testing be disseminated more widely to general internal medicine providers. Importantly it appears that certain diagnostic tests would have a much higher yield in minority populations. It is likely that resources would be better allocated if African American patients in particular were tested initially for the antiphospholipid antibodies and activated protein C resistance rather than prothrombin gene mutations or factor V Leiden. Further prospective studies are planned to confirm these findings. Baseline demographics Race Gender Age Male Female <40 years >40 years All patients 12 21 22 11 African American 6 12 11 7 White 3 5 5 3 Hispanic 1 3 4 0 Asian 2 1 2 1 Diagnosis by ethnic group Race Diagnosis Antiphospholipid Protein S def. ATIII def. V Leiden MTHFR Multiple Disorders Unknown No cases of Protein C deficiency or Prothrombin Gene Mutation identified All patients 12 3 3 1 (heterozygous) 1 2 15 African American 5 2 2 0 1 1 9 White 3 0 0 1 (heterozygous) 0 0 4 Hispanic 2 1 1 0 0 1 1 Asian 2 0 0 0 0 0 1

TREATMENT OF CONGENITAL THROMBOTIC SYNDROMES

1987 ◽  
Author(s):  
A W Broekmans ◽  
F J M der Meer ◽  
K Briët
Keyword(s):  
Pulmonary Embolism ◽  
Initial Phase ◽  
Protein C ◽  
Antithrombin Iii ◽  
Purpura Fulminans ◽  
Protein S ◽  
Protein S Deficiency ◽  
Protein C Deficiency ◽  
S Deficiency ◽  
Antithrombin Iii Deficiency

Hereditary antithrombin III deficiency,protein C deficiency, and protein S deficiency predispose to the occurrence of venous thrombotic disease at a relatively youngage and often without an apparent cause. These disorders inherit as an autosomal dominant trait. Heterozygotes are at risk fosuperficial thrombophlebitis, thrombosis atnearly every venous site, and pulmonary embolism. Homozygous protein C deficiency may present itself with a purpura fulminans syndrome shortly after birth.In the acute phase of venous thromboembolism heparin is effective for preventing extension of the thrombotic process, and pulmonary embolism. In patients with antithrombin III deficiency the concomittant useof antithrombin III concentrate is controversial, although some patients may requirehigher doses of heparin.Substitution therapy is only indicated in homozygous protein C deficient patientswith purpura fulminans. Fresh frozen plasma i.v. is the treatment of choice, in a dosage of 10 ml/kg once or twice daily. The current prothrombin complex concentrates may induce new skin lesions and disseminated intravascular coagulation. After the lesions have been healed(mostly in 4 to6 weeks)coumarin therapy may effectively prevent new episodes of purpura fulminans, provided the prothrombin time is kept within 2,5 - 4,0 INR. Heparin is ineffective for preventing purpura fulminans due to homozygous protein C deficiency.The thrombotic manifestations in heterozygotes are effectively prevented by coumarin therapy. This is supported by the observation that patients may remain free of thrombosis during long-term treatment and may have recurrences shortly after the withdrawal of the coumarin drug. The therapeutic range for the prothrombin time should be within 2,0 - 4,0 INR, target value 3,0 INR. In the initial phase of oral anticoagulant therapy protein C deficient patients are prone to the development of coumarin induced hemorrhagic skin (tissue) necrosis.In the patients studied in Leiden, it occurred in about 3% of the treated patients. Heparin appears to be ineffective for the prevention of coumarin-induced skin necrosis; high loading doses of coumarin should be avoided and the prothrombin timeshouldbe checked dialy during the initial phase of oral anticoagulant treatment. Tissue necrosis may contribute to bleeding complications after fibrinolytic therapy, ashas been observed in two protein C deficient patients.In clinical situations with an increased risk for thrombosis such as surgery and pregnancy, heparin (in-low-doses) alone orin combination with coumarins have been used succesfully for the prevention of thrombosis. The need for antithrombin III concentrates in patients with hereditary antithrombin III deficiency in such situations is not substantiated.Although anabolic steroids are capable to increase the plasma concentrations of antithrombin III and of protein C in the respective deficiency states, its efficacy in preventing thrombotic episodes remains to be established.An optimal strategy for preventing thrombosis in congenital thrombotic syndromes is to identify still asymptomatic patients. In case of antithrombin III, protein C, and protein S deficiency this search is feasible. During risk situations for thrombosis patients are to be protected against the development of thrombosis.In Leiden pregnant women with one of the deficiencies are treated from the 14th week of pregnancy, initially with a shortacting coumarin drug, after the 34th week withheparin s.c. b.i.d. at therapeutic dosages,and after delivery coumarin therapy is reTnstituted during 6 weeks. The use of oralcontraceptives should be avoided, unlesspatients are under coumarin treatment. As long as deficient patients remain asymptomatic no antithrombotic treatment is indicated. After the first documented thromboticincident patients are treated indefinitelywith oral anticoagulants.

scholarly journals Endothelial Nitric Oxide Synthase T-786C Mutation, Prothrombin Gene Mutation (G-20210-A) and Protein S Deficiency Could Lead to Myocardial Infarction in a Very Young Male Adult

2016 ◽  
Vol 4 (1) ◽  
pp. 142-145 ◽  
Author(s):  
Milka Klincheva ◽  
Elena Ambarkova Vilarova ◽  
Tanja Angjusheva ◽  
Ivan Milev ◽  
Enver Idoski ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Young Male ◽  
Protein S ◽  
Protein S Deficiency ◽  
Male Adult ◽  
S Deficiency ◽  
Prothrombin Gene Mutation ◽  
Young Male Adult ◽  
Prothrombin Gene

INTRODUCTION: Myocardial infarction is a rare medical event in young people. The main reasons include congenital coronary abnormalities, coronary artery spasm, and coronary thrombosis due to hypercoagulable states (hereditary and acquired).AIM: We present a case of a young male adult with myocardial infarction caused by a combination of gene mutations and anticoagulation protein deficiency.CASE PRESENTATION: A 19 years old young man was admitted to our hospital complaining of chest pain during the last two weeks. The patient did not have any known cardiovascular risk factors, except a positive family anamnesis. Subacute inferior nonST segment myocardial infarction was diagnosed according to the patient’s history, electrocardiographic and laboratory findings. Coronary angiography revealed suboclusive thrombus in the proximal, medial and distal part of the right coronary artery (TIMI 2). Percutaneous coronary intervention was performed. Anticoagulant and antiagregant therapy (heparin, acetilsalicilic acid and clopidogrel) according to protocol was started. The hospital stay was uneventful. Homozygous endothelial nitric oxid synthase (eNOS) T-786-C mutation, heterozygote prothrombin gene mutation (G-20210-A), and protein S deficiency were verified from the thrombophilia testing. Other trombophilic tests were normal. Three months after discharge from hospital another coronary angiography was performed. It revealed normal coronary arteries. Four years after the attack, the patient is free of symptoms and another cardiovascular event.CONCLUSION: Combination of genetic mutations and anticoagulation protein deficiency could be a reasonable cause for myocardial infarction in a very young male adult without any other cardiovascular risk factors.

Severe Arterial Cerebral Thrombosis in a Patient with Protein S Deficiency (Moderately Reduced Total and Markedly Reduced Free Protein S): A Family Study

1989 ◽  
Vol 61 (01) ◽  
pp. 144-147 ◽  
Author(s):  
A Girolami ◽  
P Simioni ◽  
A R Lazzaro ◽  
I Cordiano
Keyword(s):  
Arterial Thrombosis ◽  
Protein C ◽  
Protein S ◽  
Protein S Deficiency ◽  
Protein C Deficiency ◽  
Free Protein ◽  
Her Family ◽  
S Deficiency ◽  
Increased Risk ◽  
Patient Reported

SummaryDeficiency of protein S has been associated with an increased risk of thrombotic disease as already shown for protein C deficiency. Deficiencies of any of these two proteins predispose to venous thrombosis but have been only rarely associated with arterial thrombosis.In this study we describe a case of severe cerebral arterial thrombosis in a 44-year old woman with protein S deficiency. The defect was characterized by moderately reduced levels of total and markedly reduced levels of free protein S. C4b-bp level was normal. Protein C, AT III and routine coagulation tests were within the normal limits.In her family two other members showed the same defect. All the affected members had venous thrombotic manifestations, two of them at a relatively young age. No other risk factors for thrombotic episodes were present in the family members. The patient reported was treated with ASA and dipyridamole and so far there were no relapses.

Factor V Leiden: An Additional Risk Factor for Thrombosis in Protein S Deficient Families?

1995 ◽  
Vol 74 (02) ◽  
pp. 580-583 ◽  
Author(s):  
B P C Koeleman ◽  
D van Rumpt ◽  
K Hamulyák ◽  
P H Reitsma ◽  
R M Bertina
Keyword(s):  
Protein C ◽  
Normal Population ◽  
Factor V Leiden ◽  
Protein S ◽  
Reliable Estimate ◽  
Additional Risk Factor ◽  
Protein S Deficiency ◽  
S Deficiency ◽  
High Prevalence ◽  
Fv Leiden

SummaryWe recently reported a high prevalence of the FV Leiden mutation (R506Q, responsible for Activated Protein C resistance) among symptomatic protein C deficient probands (19%), and the involvement of the FV Leiden mutation in the expression of thrombophilia in six protein C deficient families. Here, we report the results of a similar study in protein S deficient probands and families. Among 16 symptomatic protein S deficient probands the prevalence of the FV Leiden mutation was high (38%). This high prevalence is significantly different from that in the normal population, and is probably caused by the selection of probands for familial thrombosis and protein S deficiency. In 4 families, the segregation of the FV Leiden mutation and the protein S deficiency could be studied. In sibships where both abnormalities were segregating, the percentage of symptomatic individuals with both abnormalities was 80%. Three of the seven subjects with only the FV Leiden mutation, and two out of the three subjects with only protein S deficiency had developed thrombosis. These results indicate that in the families presented here the combination of the FV Leiden mutation and the protein S deficiency is associated with a high risk for thrombosis. A reliable estimate of the penetrance of the single defects is not possible, because the number of individuals with a single defect is too low.

Elevated Levels of Prothrombin Activation Fragment 1+2 in Plasma from Patients with Heterozygous Arg506 to Gin Mutation in the Factor V Gene (APC-Resistance) and/or Inherited Protein S Deficiency

1996 ◽  
Vol 75 (02) ◽  
pp. 270-274 ◽  
Author(s):  
Benget Zöller ◽  
Johan Holm ◽  
Peter Svensson ◽  
Björn Dahlbäck
Keyword(s):  
Plasma Concentration ◽  
Protein C ◽  
Protein S ◽  
Factor V ◽  
Protein S Deficiency ◽  
Apc Resistance ◽  
S Deficiency ◽  
Increased Risk ◽  
Factor V Gene ◽  
V Gene

SummaryInherited resistance to activated protein C (APC-resistance), caused by a point mutation in the factor V gene leading to replacement of Arg(R)506 with a Gin (Q), and inherited protein S deficiency are associated with functional impairment of the protein C anticoagulant system, yielding lifelong hypercoagulability and increased risk of thrombosis. APC-resistance is often an additional genetic risk factor in thrombosis-prone protein S deficient families. The plasma concentration of prothrombin fragment 1+2 (F1+2), which is a marker of hyper-coagulable states, was measured in 205 members of 34 thrombosis-prone families harbouring the Arg506 to Gin mutation (APC-resistance) and/or inherited protein S deficiency. The plasma concentration of F1+2 was significantly higher both in 38 individuals carrying the FV:Q506 mutation in heterozygous state (1.7 ± 0.7 nM; mean ± SD) and in 48 protein S deficient cases (1.9 ± 0.9 nM), than in 100 unaffected relatives (1.3 ±0.5 nM). Warfarin therapy decreased the F1+2 levels, even in those four patients who had combined defects (0.5 ± 0.3 nM). Our results agree with the hypothesis that individuals with APC-resistance or protein S deficiency have an imbalance between pro- and anti-coagulant forces leading to increased thrombin generation and a hypercoagulable state.

scholarly journals The A20210 Allele of the Prothrombin Gene Is Frequently Associated With the Factor V Arg 506 to Gln Mutation But Not With Protein S Deficiency in Thrombophilic Families

Blood ◽  
1998 ◽  
Vol 91 (6) ◽  
pp. 2210-2211 ◽  
Author(s):  
Bengt Zöller ◽  
Peter J. Svensson ◽  
Björn Dahlbäck ◽  
Andreas Hillarp
Keyword(s):  
Protein S ◽  
Factor V ◽  
Protein S Deficiency ◽  
S Deficiency ◽  
Prothrombin Gene
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