scholarly journals Compound Homozygous Factor V Leiden and Heterozygous Prothrombin Gene Mutation: The First Report in a Pregnant African with Extensive Thrombosis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5056-5056
Author(s):  
Livingstone Gayus Dogara ◽  
Joseph Ogirima Ovosi ◽  
Caleb Mohammed ◽  
Bilkisu Farouk ◽  
Ziphozonke Mafika ◽  
...  
Keyword(s):  
Blood Cells ◽  
Research Funding ◽  
Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
African Countries ◽  
C Protein ◽  
History Of ◽  
In Pregnancy

Abstract Background: Factor V Leiden (FVL) mutation and Protein gene G20210A mutation (PGM) are the most common inherited thrombophilias in the world. (Limdi NA et.al, Blood Cells Mol Dis. 2006 Sep-Oct;37(2):100-6) Both are inherited in an autosomal recessive fashion with individuals who are homozygous having higher risk of thrombosis compared to those who are heterozygous.(Rodger MA et.al, PLoS Med. 2010 Jun 15;7(6):e1000292.) The global prevalence of FVL and PGM is variable with Caucasians carrying the highest prevalence and Africans living in Africa, Asians and Native Americans having the lowest rate of these mutations; it is zero in West and Southern African countries, 2.4%-3.9% in North African countries including Morocco, Tunisia, and Algeria. (Limdi NA et.al, Blood Cells Mol Dis. 2006 Sep-Oct;37(2):100-6, Dziadosz M et. al, Blood Coagul Fibrinolysis. 2016 Jul;27(5):481-9) Pregnancy increases the risk of developing venous thromboembolism (VTE) by 0.05-1.8 %, (Eldor A, Thromb Haemost. 2001 12.12.2017;86(07):104-11) which is 4 to 5 fold greater than in non-pregnant female.(Croles FN et.al, BMJ. 2017;359, Greer IA, N Engl J Med. 2015 Aug 6;373(6):540-7) Inheritance of FVL and PGM increases the risk for development of VTE in pregnancy, the risk is higher with homozygous than heterozygous mutations.(Rodger MA et.al, PLoS Med. 2010 Jun 15;7(6):e1000292.) Concurrent presentation of FVL and PGM in pregnancy presenting as thrombosis is not common. Aim: The aim of this case report is to present a patient of African descent with concurrent FVL and PGM mutation who had thrombosis during pregnancy. The Case: A 32-year-old Nigerian female who was 28 weeks pregnant presented to the gynecologist with a swollen left leg. Physical examination and the Wells score were very suggestive of a deep vein thrombosis (DVT). The Duplex Doppler performed confirmed a diagnosis of bilateral lower limb DVT. The patient was referred to a physician, who together with the haematologist performed a thrombophilia screen including FVL, PGM, Protein C, Protein S and Anticardiolipin antibody tests. The D-DIMERS were raised and the viral markers including HIV, HBV, and HCV were negative. The PT, APTT and full blood counts were normal. The thrombophilia tests revealed that the patient was homozygous for FVL and also heterozygous for the PGM mutations. The rest of the thrombophilia screen including Protein C, Protein S and Antithrombin tests were all negative. She has no family history of thrombosis; no past history of hormone based contraceptives. She was counselled on the need for using anticoagulation, low molecular weight heparin (LMWH) during the rest of her pregnancy period, and therapeutic anticoagulation with a LMWH at a dose of 1mg/kg twice a day until onset of labour was started. During labour LMWH was discontinued, delivery was per vaginal and was uncomplicated. Postpartum LMWH was continued at therapeutic doses for six weeks with no bleeding or thrombotic events. After six weeks, the patient was started on lifelong warfarin. Results (See Table) Discussion: To our knowledge this is a first case of a patient born and living in Africa presenting with thrombosis and found to have homozygous FVL and heterozygous PGM during pregnancy, the one report that is similar was in a second generation South African woman of German, Dutch and French ancestry. (Wilson J et. al, Medical Technology SA. [Case Report]. December 2011;25(2):4) Most reports have shown ethnic and regional affectation. (Limdi NA et.al, Blood Cells Mol Dis. 2006 Sep-Oct;37(2):100-6, Bavikatty NR, et.al, Am J Clin Pathol. 2000 Aug;114(2):272-5) There is no single agreed reason as to why the mutation is rare in Africa though founder effect is being studied to define how the mutation came about, it could have taken place before divergence of race. (Jadaon MM. [Thrombosis, Familiar Thrombophilia]. 2011 2011-11-28;3(1) We could not do family studies to help define the origin of this mutation whether it is denovo for Nigeria; this has to do with sentiments about genetic inheritance in Africa. Conclusion: Concurrent inheritance of both FVL and PGM is possible in Africa. This rare case has open opportunities to revisit the prevalence of thrombophilia in Nigeria and other African countries. Disclosures Mahlangu: Alnylam: Consultancy, Research Funding, Speakers Bureau; Biomarin: Research Funding, Speakers Bureau; Catalyst Biosciences: Consultancy, Research Funding; Chugai: Consultancy; Amgen: Consultancy; Bayer: Research Funding; Biogen: Research Funding, Speakers Bureau; CSL Behring: Consultancy, Research Funding, Speakers Bureau; NovoNordisk: Consultancy, Research Funding, Speakers Bureau; LFB: Consultancy; Roche: Consultancy, Research Funding, Speakers Bureau; Sanofi: Research Funding, Speakers Bureau; Shire: Consultancy, Research Funding, Speakers Bureau; Sobi: Research Funding, Speakers Bureau; Spark: Consultancy, Research Funding.

scholarly journals Thrombophilia And Arterial Ischemic Stroke

2017 ◽  
pp. 45
Author(s):  
A.A. Abrishamizadeh
Keyword(s):  
Ischemic Stroke ◽  
Vitamin K ◽  
Arterial Thrombosis ◽  
Protein C ◽  
Antithrombin Iii ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
C Protein

Ischemic stroke (IS) is a common cause of morbidity and mortality with significant socioeconomic impact especially when it affects young patients. Compared to the older adults, the incidence, risk factors, and etiology are distinctly different in younger IS. Hypercoagulable states are relatively more commonly detected in younger IS patients.Thrombophilic states are disorders of hemostatic mechanisms that result in a predisposition to thrombosis .Thrombophilia is an established cause of venous thrombosis. Therefore, it is tempting to assume that these disorders might have a similar relationship with arterial thrombosis. Despite this fact that 1-4 % of ischemic strokes are attributed to Thrombophillia, this   alone rarely causes arterial occlusions .Even in individuals with a positive thrombophilia screen and arterial thrombosis, the former might not be the primary etiological factor.Thrombophilic   disorders can be broadly divided into inherited or acquired conditions. Inherited thrombophilic states include deficiencies of natural anticoagulants such as protein C, protein S, and antithrombin III (AT III) deficiency, polymorphisms causing resistance to activated protein C(Factor V Leiden mutation), and disturbance in the clotting balance (prothrombin gene 20210G/A variant). Of all the inherited  thrombophilic disorders, Factor V Leiden mutation is perhaps the commonest cause. On the contrary, acquired thrombophilic disorders are more common and include conditions such as the antiphospholipid syndrome, associated with lupus anticoagulant and anticardiolipin antibodies.The more useful and practical approach of ordering various diagnostic tests for the uncommon thrombophilic states tests should be determined by a detailed clinical history, physical examination, imaging studies and evaluating whether an underlying hypercoagulable state appears more likely.The laboratory thrombophilia   screening should be comprehensive and avoid missing the coexisting defect and It is important that a diagnostic search protocol includes tests for both inherited and acquired thrombophilic disorders.Since the therapeutic approach (anticoagulation and thrombolytic therapy) determines the clinical outcomes, early diagnosis of the thrombophilic  disorders plays an important role. Furthermore, the timing of test performance of some of the  thrombophilic  defects (like protein C, protein S, antithrombin III and fibrinogen levels) is often critical since these proteins can behave as acute phase reactants and erroneously elevated levels of these factors may be observed in patients with acute thrombotic events. On the other hand, the plasma levels of vitamin K-dependent proteins (protein C, protein S and APC resistance) may not be reliable in patients taking vitamin K antagonists. Therefore, it is suggested that plasma-based assays for these disorders should be repeated3 to 6 months after the initial thrombotic episode to avoid false-positive results and avoid unnecessary prolonged   anticoagulation therapy. The assays for these disorders are recommended after discontinuation of oral anticoagulant treatment or heparin for at least 2 weeks.    

Fundamentals and Patient Evaluation

2006 ◽  
Author(s):  
Richard C. Becker ◽  
Frederick A. Spencer
Keyword(s):  
General Population ◽  
Venous Thrombosis ◽  
Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Incidence Rates ◽  
Factor V ◽  
Inherited Thrombophilia ◽  
Occult Malignancy ◽  
History Of

Thrombophilia is the term used to describe a tendency toward developing thrombosis. This tendency may be inherited, involving polymorphism in gene coding for platelet or clotting factor proteins, or acquired due to alterations in the constituents of blood and/or blood vessels. An inherited thrombophilia is likely if there is a history of repeated episodes of thrombosis or a family history of thromboembolism. One should also consider an inherited thrombophilia when there are no obvious predisposing factors for thrombosis or when clots occur in a patient under the age of 45. Repeated episodes of thromboembolism occurring in patients over the age of 45 raise suspicion for an occult malignancy. A summary of inherited thrombophilias are summarized in Table 24.1. This list continues to grow, as new genetic polymorphisms and combined mutations are being detected. The prevalence of common thrombophilias is shown in Figure 24.1. Factor V Leiden (FVL) mutation and hyperhomocysteinemia are present in nearly 5% of the general population and are often found in patients with venous thrombosis, while deficiencies of antithrombin (AT), protein C, and protein S are relatively uncommon. Elevated levels of factor VIII (FVIII) are uncovered frequently in the general population and in patients with thrombosis. This is not surprising as FVIII is an acute-phase reactant that increases rapidly after surgery or trauma; however, prospective studies have shown that FVIII elevation in some patients cannot be attributed to a stress reaction and probably represents mutations in the genes regulating FVIII synthesis or release (Kyrle et al., 2000). The same may be true for factors IX and XI. The relative risks for thrombosis among patients with inherited thrombophilias have been determined. While AT mutations are the least common, they are associated with a substantial risk of venous thrombosis; similar risk is seen with protein C and S deficiency. In contrast, the lifetime risk of having a thromboembolic event in an individual heterozygous for FVL is comparatively low (Martinelli et al., 1998). Incidence rates markedly increase with age, and are highest among those with AT deficiency, followed by protein C and protein S, and least with FVL.

4g/5g Prevalence in 223 Patients with Thrombosis and in 162 Healthy Controls, from the Centre Region of Portugal.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4057-4057
Author(s):  
Rosa Maia ◽  
Emilia Cortesao ◽  
Catarina Geraldes ◽  
Luis Simoes ◽  
Carla Simoes ◽  
...  
Keyword(s):  
Protein C ◽  
Antithrombin Iii ◽  
Factor V Leiden ◽  
Protein S ◽  
Mthfr C677t ◽  
Insertion Polymorphism ◽  
Factor V ◽  
Centre Region ◽  
History Of ◽  
Pai 1

Abstract A deletion/insertion polymorphism (4G or 5G) in the promoter of the PAI-1 gene has been suggested to be involved in regulation of the synthesis of the inhibitor, the 4G allele being associated with enhanced gene expression, and therefore related with thrombosis. In the present work we studied the prevalence of 4G/5G polymorphism in 223 unrelated patients with history of objectively confirmed thromboembolism, and in 162 healthy unrelated controls, both groups natural from all centre regions of Portugal. In this normal cohort, the prevalence of 4G/4G is 23%, 4G/5G is 38% and 5G/5G is 39%; in the affected population is, respectively, 47%, 21.5% and 30%, which means that 4G/4G is twice more frequent in the patients with thrombosis. When we relate the age of the first thrombosis episodes in the three groups, we find no significative difference, as the respective media is 36.8; 38.6 and 35.5 years in the 4G/4G, 4G/5G and 5G/5G group, respectively. This data suggest that this polymorphism by itself, even in homozygosity, is not associated with earlier thrombosis. In our patients, we studied the presence of Lupus Anticoagulant, Factor V Leiden, Factor IIG20210A, MTHFR C677T, and also Antithrombin III, Protein S and Protein C levels. We analyse the prevalence of the three mutations in patients with DVP, PTE, ischemic and venous CVA and we only find a significative difference in the 4G/4G group: 46.2% patients with DVP and 48.2% patients with PTE (23% in normal cohort). In conclusion, in the centre region of Portugal, the prevalence of 4G/4G is 23%, 4G/5G is 38% and 5G/5G is 39%; in our cohort of unrelated patients the only significative difference is in the 4G/4G group (47%); this variation maintain in the DVP and PTE group. We did not find difference at the age of the first thrombotic episode, in the three groups.

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

Activated Protein C Sensitivity, Protein C, Protein S and Coagulation in Normal Pregnancy

1998 ◽  
Vol 79 (06) ◽  
pp. 1166-1170 ◽  
Author(s):  
J. Brennand ◽  
J. A. Conkie ◽  
F. McCall ◽  
I. A. Greer ◽  
Isobel Walker ◽  
...  
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Coagulation Factors ◽  
Normal Pregnancy ◽  
Factor V ◽  
C Protein ◽  
Sensitivity Ratio ◽  
Protein C Activity

SummaryA prospective study of activated protein C sensitivity, protein C, protein S, and other coagulation factors in 239 women during normal pregnancy was carried out. Protein C activity appeared unaffected by gestation, although an elevation of protein C activity was observed in the early puerperium. A fall in total and free protein S with increasing gestation was observed. Activated protein C sensitivity ratio (APC:SR) showed a progressive fall through pregnancy. This fall correlated with changes in factor VIIIc, factor Vc and protein S. 38% of subjects, with no evidence of Factor V Leiden or anticardiolipin antibodies, showed a low APC:SR (APC:SR <2.6) in the third trimester of pregnancy. Aside from a significant reduction in birth weight, no difference in pregnancy outcome was observed between these subjects and those with a normal APC:SR. Activated protein C sensitivity ratio, modified by pre-dilution of patient samples with factor V depleted plasma, showed no consistent trend with gestation.

Inherited Prethrombotic Disorders and Infectious Purpura

1996 ◽  
Vol 75 (06) ◽  
pp. 899-901 ◽  
Author(s):  
Rudi G J Westendorp ◽  
Pieter H Reitsma ◽  
Rogier M Bertina
Keyword(s):  
Risk Factors ◽  
Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Disease Course ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
C Protein ◽  
Severity Of The Disease

SummaryPatients with severe meningococcal infection are characterized by extensive microvascular thrombosis, consumption coagulopathy and secondary hemorrhages. The contribution of the inherited prethrombotic disorders to the severity of the disease course is not established yet. Here, we report on the levels of protein C, protein S, antithrombin and the presence of the factor V Leiden mutation (R506Q) in 50 patients with meningococcal disease, as determined 6 to 58 months after hospital discharge. In addition, we recalled the parents of 16 deceased patients to screen for the mutation in factor V, an abnormality which results in resistance to activated protein C. Among the patients, the prevalence of the genetic risk factors for thrombosis was not higher than expected on the basis of their prevalence in the general population. Moreover, the prevalence of the factor V Leiden mutation was not increased among the parents of the deceased patients. The individual plasma levels of protein C, protein S, and antithrombin did not differ between the patients with or without severe purpura. The present data constitute circumstantial evidence that primary defects in the natural anticoagulant systems do not play a major role in the severity of the disease course. Screening of patients with infectious purpura for inherited thrombotic risk factors is therefore not indicated.

Thrombophilia in Pathological Pregnancies

2016 ◽  
Vol 70 (3) ◽  
pp. 129-132
Author(s):  
Jani Angelovski
Keyword(s):  
High Risk ◽  
Factor V Leiden ◽  
Protein S ◽  
Cross Sectional Study ◽  
Intrauterine Fetal Death ◽  
Factor V ◽  
Cross Sectional ◽  
Protective Function ◽  
History Of ◽  
In Pregnancy

Abstract Introduction. Many situations in pregnancy create a thrombophilia, which is believed to have a protective function, which is the result of the hormone influence, primarily by gestagenic hormones. This is a physiological condition and it helps in successful implantation of the embryo and prevention of bleeding. The presence of additional, hereditary or acquired cause of thrombophilia disrupts the natural balance and creates conditions for venous thromboembolism and consequences for pregnancy, such as miscarriage, intrauterine fetal death, delayed intrauterine growth, eclampsia and abruption of the placenta. Methods. The study was designed as a retrospective epidemiological cross-sectional study and was conducted at the Institute of Transfusion Medicine in Skopje in the period from June to October 2016. The study included patients with current pathological pregnancies. The following laboratory analyses were conducted in all patients: hemostasis, D-dimer, antithrombin III, protein C, protein S, antiphospholipid antibodies, lupus anticoagulant, MTHFR, factor V Leiden and prothrombin mutation. Results. The study included 41 patients, of whom 3 were excluded due to an insufficient medical history, 3 who were receiving corticosteroid therapy, 2 due to incomplete laboratory analyses and one patient with proven systemic lupus. Data analysis showed that family history of thrombophilia was present in 25%. The most common MTHFR mutation was recorded in 26 (82%) patients, followed by the factor V mutation present in 18 (55%) of the examined patients. AT III deficiency was detected in only one patient (2%). In 12 patients (35%) a disturbed ratio of DD vs. markedly shortened APTT or inappropriately low levels of DD was registered, which is an indirect indicatorof hypofibrinolysis. Conclusion. Pathologic pregnancy is a condition that is often associated with thrombophilia. Advanced age of a patient, family and personal history of thrombotic conditions indicate a high risk of complications in pregnancy. Due to the current increased frequency of high risk pregnancies associated with circulation problems with the placenta, there is a need for more frequent hemostatic examinations in pregnancy.

scholarly journals Primary Thrombophilia in Mexico: A Single Tertiary Referral Hospital Experience

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4717-4717
Author(s):  
Dennis Lacayo-Leñero ◽  
Angel Gabriel Vargas-Ruiz ◽  
Olga Barrales-Benítez ◽  
Darinel Hernández-Hernández ◽  
Andrés Valencia-Martínez
Keyword(s):  
Protein C ◽  
Age At Onset ◽  
Factor V Leiden ◽  
Protein S ◽  
Mthfr C677t ◽  
Factor V ◽  
Tertiary Referral Hospital ◽  
Unusual Site ◽  
Mthfr C677t Polymorphism ◽  
History Of

Abstract Background: Thrombophilia is a complex hypercoagulable state that predisposes to thrombosis. Several thrombophilia reports have been conducted in Mexicans with lack of statistical significance. The objective of this study was to describe the prevalence of primary thrombophilia in a tertiary referral hospital in Mexico. Material and methods: Retrospective study of patients referred for primary thrombophilia between January 2011 and May 2015.. Thrombophilia study included: MTHFR C677T, anti-phopholipid antibodies, protein C, protein S, antithrombin, factor VIII, factor V Leiden, prothrombin mutation G20210A, APCR, JAK2 V617F, homocysteine. We used descriptive statistics according to the distribution of the variables. We used measures of central tendency and dispersion: average, median. All analyses were performed using the SPSS for Windows 20.0® Results: We identified 224 patients referred for thrombophilia testing in a 4 year period. At the time of statistical analysis 129 patients were excluded for lacking data.Ninety five patients were included.Median age at onset was 36 years. (Table 1) Nine of 60 (15%) female patients reported previous use of contraceptives and 13/60 (21.6%) reported previous obstetric morbidity. (Table 2). We identified at least one anomaly related with thrombophilia in 90/95 patients (94.7%). Eighty patients (84.1%) presented the MTHFR C677T polymorphism; heterozygous 51/95 (53.6%) presenting with hyperhomocysteinemia 18/51 (35.2%) and homozygous 29/95 (30.5%) presenting with hyperhomocysteinemia 10/29 (34.4%).Factor V Leiden was found in 5/95 (5.2%) heterozygous. It co-occurred with APCR in 3/5 cases (60%).In 44 patients we found an isolated anomaly associated with thrombophilia (46.3%). In 51/95 (53.6%) we identified co-occurring anomalies associated with thrombophilia. (Table 3). The median of co-occurring anomalies was 2 (2-4). Conclusions: The MTHFR C677T polymorphism has a very high prevalence in Mexicans compared to the low prevalence of anticoagulant protein deficiency and factor V Leiden mutation. Table 1. Demographic characteristics. Demographic characteristics No. Patients (%) -Gender Male Female Total 35 (36.8) 60 (63.1) 95 (100) -Age Median years (range) 36 (17-75) -Family history of thrombosis -Cardiovascular risk factors Arterial Hypertension Diabetes mellitus Dyslipidemia Smoking 15 (15.7) 13 (13.6) 11 (11.5) 13 (13.6) 15 (15.7) -Surgery related thrombosis 3 (3.1) -Cancer related thrombosis 3 (3.1) -Autoimmune disease SLE Other autoimmune disease 11 (11.5) 3 (3.1) 8 (8.4) SLE: Systemic Lupus Erythematosus. Table 2. Thrombosis characteristics. Thrombosis characteristics No. Patients (%) -Thrombotic events Median (range) 1 (1-4) -Affected territory Venous Arterial Mixed 80 (84.2) 14 (14.7) 1 (1) -Thrombophilia testing indication Age at onset <45 years. Family history of thrombosis Unusual site thrombosis Intra abdominal thrombosis Cerebral vein thrombosis Other unusual site thrombosis Recurrent thrombosis Obstetric morbidity More than one indication for testing 91 (95.7) 77 (81) 15 (15.7) 48 (50.5) 25/48 (52) 11/48 (22.9) 12/48 (25) 26 (27.3) 13/60 (21.6) 62 (65.2) -Treatment VKA LMWH Clopidogrel NOAC's ASA None ND 44 (46.3) 3 (3.1) 1 (1) 8 (8.4) 14 (14.7) 6 (6.3) 19 (20) VKA: Vitamin K Antagonist LMWH: Low Molecular Weight Heparin; NOAC's: New oral anticoagulants; ASA: acetylsalicylic acid. ND: Not described. Table 3. Results of thrombophilia anomalies. TROMBOPHILIA TOTAL FREQUENCY ISOLATED FREQUENCY CO-OCCURRING WITH ANOTHER THROMBOPHILIA ANOMALY. -MTHFR C677T heterozygous 51/95 (53.6%). 22/51 (43.1%) 29/51 (56.8%) -Hyperhomocysteinemia 36/95 (37.8%). 6/36 (16.6%) 30/36 (83.3%) -MTHFR C677T homoczygous 29/95 (30.5%). 14/29 (48.2%) 15/29 (51.7%) -APCR 13/95 (13.6%). 0 13/13 (100%) -F V Leiden G1691A 5/95 (5.2%) 0 5/5 (100%) -Protein C deficiency 5/95 (5.2%) 0 5/5 (100%) -Elevated FVIII levels (>150%) 4/95 (4.2%) 0 4/4 (100%) -Protein S deficiency 3/95 (3.1%) 1/3 (33.3%) 2/3 (66.6%) -APS 3/95 (3.1%) 0 3/3 (100%) -Prothrombin G20210A 2/95 (2.1%). 0 2/2 (100%) -JAK2V617F 1/95 (1.0%) 1/1 (100%) 0 -Antithrombin deficiency 0 0 0 MTHFR: methylentetrahidrofolate reductase; APCR: Activated protein C resistance; APS: Antiphospholipid syndrome. Disclosures No relevant conflicts of interest to declare.

Improved Detection of FV Leiden Patients Using a Novel Snake-Venom-Based Activated Protein C Resistance Assay.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1058-1058
Author(s):  
Marianne Wilmer ◽  
Christoph Stocker ◽  
Beatrice Buehler ◽  
Brigitte Conell ◽  
Andreas Calatzis
Keyword(s):  
Snake Venom ◽  
Lupus Anticoagulant ◽  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
C Protein ◽  
Apc Resistance ◽  
Thrombophilia Screening

Abstract A new functional prothrombin-based activated protein C (APC) resistance (APC-R) test (Pefakit® APC-R Factor V Leiden, Pentapharm, Basel, Switzerland) is presented. Methods: The plasma sample is mixed with a reagent containing APC and snake venom specifically activating FV (RVV-V, Daboia russelli) and plasma that has been depleted of FV. During an incubation period of 180 sec the activated FV is inactivated by APC. Subsequently a reagent that contains a FV dependent prothrombin activator (Noscarin, Notechis scutatus) and EDTA is added. The clotting time is recorded. A second determination is performed under identical conditions, with the exception that no APC is added to the first reagent. A ratio between the two measurements is calculated. 703 samples of patients undergoing thrombophilia screening were analysed. Results were correlated to PCR based FVL testing, aPTT, PT, and to levels of Protein C, Protein S, Fibrinogen, FVIII and lupus anticoagulant index. Results: Using a predefined cut-off of a ratio of 2.5 a 100% sensitivity and specificity for the detection of a FVL mutation was found. Using a cut-off ratio of 1.2 a complete but narrow distinction of FVL heterozygous (n=192) and FVL homozygous samples (n=27) was determined. No interference by sample’s INR and aPTT, PS, fibrinogen and FVIII levels and lupus anticoagulant ratio was detected. Conclusion: The new snake-venom-based APC-R assay provides an improved distinction of FV wild-type and FVL carriers compared to the data reported for the aPTT based methods. The use of a FV dependent prothrombin activator eliminates effects of FVIII concentration or lupus anticoagulants in the sample.

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