Autosomal Recessive Inherited Bleeding Disorders in Pakistan, a Cross Sectional Study from Selected Regions

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4708-4708
Author(s):  
Arshi Naz ◽  
Mohammad younus Jamal ◽  
Samina Tufail Amanat ◽  
Humayun Patel ◽  
Akbar Agha ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Cross Sectional Study ◽  
Factor V ◽  
Bleeding Disorders ◽  
Clotting Factors ◽  
Cross Sectional ◽  
Glanzmann Thrombasthenia ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract INTRODUCTION: Incidence of autosomal recessive disorders is rare, includes deficiencies of clotting factors I, II, V, VII, X, XI, XIII, vitamin K dependent clotting factors, combined factor V & VIII, Von Willebrand disease type 3, Glanzmann Thrombasthenia and Bernard Soulier syndrome. OBJECTIVE: Spectrum of autosomal recessive bleeding disorders (ARBDs] among Pakistani patients. PATIENTS AND METHODS: This cross-sectional study was carried out at Karachi, Lahore, Islamabad and Peshawar. PT,aPTT, BT, and fibrinogen levels done. Patients with prolonged APTT were tested for factors VIII and IX. If FVIII was low, von Willebrand factor: antigen (vWF: Ag) and von Willebrand factor: ristocetin cofactor (vWF: RCo) were performed. When PT and aPTT both were prolonged, FII, FV, and FX were tested. Peripheral film and platelet aggregation studies were done for platelet disorders. Urea clot solubility test was done at the end. RESULTS: Out of429 patients, 148 were diagnosed with Hemophilia A, remaining 281 patients had ARBDs. 95 (33.8%) had VWD type 3. Fibrinogen deficiency was found in 34 (12%), Glanzmann Thrombasthenia in 27 (9.6%), factor XIII in 13 (4.6%), factor VII in 12 (4.3%), factor V in 9 (3.2%), 8 (2.8%) in vitamin K dependent clotting factors, , Bernard Soulier in 7 patient (2.5%),factor X in 2 (0.7%), factor II in 2 (0.7%), factor XI and combined factor V and VIII in 1 (0.4%)patients each. 70 patients (16.3%) remained undiagnosed. CONCLUSION: VWD type 3 is the most common deficiency followed by fibrinogen deficiency. Glanzmann thrombasthenia was the third most common ARBD. Disclosures No relevant conflicts of interest to declare.

von Willebrand factor-cleaving protease (ADAMTS13) activity in normal non-pregnant women, pregnant and post-delivery women

2004 ◽  
Vol 92 (12) ◽  
pp. 1320-1326 ◽  
Author(s):  
Cristina Farías ◽  
María Amaral ◽  
Ana Kempfer ◽  
Roberto Votta ◽  
Carlos Marchese ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Von Willebrand Factor ◽  
Normal Pregnancy ◽  
Cross Sectional Study ◽  
Adamts13 Activity ◽  
Thrombotic Microangiopathies ◽  
Cross Sectional ◽  
Contraceptive Pills ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryADAMTS13 dysfunction has been involved in the pathogenesis of Thrombotic Thrombocytopenic Purpura. This disorder occurs more frequently in women and, in 13% of them, is associated with pregnancy. However, there is little information on the protease behaviour in normal pregnancy. We studied von Willebrand factor and ADAMTS13 activity changes in normal non-pregnant, pregnant and post-delivery women. Fifty-five non-pregnant women, normal blood bank donors, who were not taking contraceptive pills were included as controls. A prospective cross-sectional study of 270 normal pregnant and post-delivery women was carried out. ADAMTS13 activity decreased progressively as from the period of 12–16 weeks up to the end of early puerperium (mean 52%, range 22–89, p < 0.0001), to increase slightly thereafter. Nulliparous presented mildly lower levels of ADAMTS13 activity than parous women (65% vs. 83%, p=0.0003), and primigravidae than multigravidae between 6–11 weeks up to 17–23 weeks of pregnancy (69% vs. 80%, p=0.005). Although in all women the protease levels were the same by blood groups, the O blood group non-pregnant women showed a higher mean of ADAMTS13 activity than those non-O (78% vs. 69%, p= 0.064). Our results suggest that the changing levels of protease activity during pregnancy and puerperium, induced by unidentified mechanisms, could render the peripartum time more vulnerable to developed thrombotic microangiopathies.

scholarly journals The Impact of Age and BMI on the VWF/ADAMTS13 Axis and Simultaneous Thrombin and Plasmin Generation in Hospitalized COVID-19 Patients

2022 ◽  
Vol 8 ◽  
Author(s):  
Kiruphagaran Thangaraju ◽  
Upendra Katneni ◽  
Imo J. Akpan ◽  
Kenichi Tanaka ◽  
Tiffany Thomas ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Virus Disease ◽  
Cross Sectional Study ◽  
Binding Activity ◽  
Adamts13 Activity ◽  
Cross Sectional ◽  
Present Cross Sectional Study ◽  
Von Willebrand ◽  
The Impact ◽  
Willebrand Factor

Aging and obesity independently contribute toward an endothelial dysfunction that results in an imbalanced VWF to ADAMTS13 ratio. In addition, plasma thrombin and plasmin generation are elevated and reduced, respectively, with increasing age and also with increasing body mass index (BMI). The severity risk of Corona Virus Disease 2019 (COVID-19) increases in adults older than 65 and in individuals with certain pre-existing health conditions, including obesity (&gt;30 kg/m2). The present cross-sectional study focused on an analysis of the VWF/ADAMTS13 axis, including measurements of von Willebrand factor (VWF) antigen (VWF:AG), VWF collagen binding activity (VWF:CBA), Factor VIII antigen, ADAMTS13 antigen, and ADAMTS13 activity, in addition to thrombin and plasmin generation potential, in a demographically diverse population of COVID-19 negative (−) (n = 288) and COVID-19 positive (+) (n = 543) patient plasmas collected at the time of hospital presentation. Data were analyzed as a whole, and then after dividing patients by age (&lt;65 and ≥65) and independently by BMI [&lt;18.5, 18.5–24.9, 25–29.9, &gt;30 (kg/m2)]. These analyses suggest that VWF parameters (i.e., the VWF/ADAMTS13 activity ratio) and thrombin and plasmin generation differed in COVID-19 (+), as compared to COVID-19 (−) patient plasma. Further, age (≥65) more than BMI contributed to aberrant plasma indicators of endothelial coagulopathy. Based on these findings, evaluating both the VWF/ADAMTS13 axis, along with thrombin and plasmin generation, could provide insight into the extent of endothelial dysfunction as well as the plasmatic imbalance in coagulation and fibrinolysis potential, particularly for at-risk patient populations.

Reliability of Plasma Von Willebrand Factor Antigen in Prediction of Oesophageal Varices in Pediatric and Adolescent Patients with Portal Hypertension

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Lerine B Eldin ◽  
Asmaa W Abd Elaziz ◽  
Dina A Ragab ◽  
Karim A Abdelhady
Keyword(s):  
Portal Hypertension ◽  
Cross Sectional Study ◽  
Oesophageal Varices ◽  
Sectional Study ◽  
Cross Sectional ◽  
Non Invasive ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Larger Sample ◽  
Factor Antigen

Abstract Background Ruptured oesophageal varices (OVs) is a major cause of mortality in Portal hypertension (PHT) patients, It has been a great issue of interest and research to screen and early detect OVs via oesophageal varices non-invasive methods. Objective The aim of this study was to assess the reliability of measuring plasma von willibrand factor antigen (VWF-Ag) for prediction of the occurrence of oesophageal varices in patients with portal hypertension. Subjects & Methods This was a prospective cross-sectional study, done on 47 children with portal hypertension. The children were recruited from Pediatrics Hepatology clinic, Ain Shams University. Patient’s data was collected including age, sex, etiology and duration of PHT, along with medical treatment. Also an upper GIT endoscope, abdominal doppler ultrasound, and laboratory tests including measuring of plasma VWF-Ag were done to each patient. Then the children were divided based on their endoscopic findings into two groups; variceal group which included 37 patients, and a nonvariceal group which included 10 patients Results: The results of our study revealed an elevated plasma VWF-Ag in patients with oesophageal varices, whilst normal levels of plasma VWF-Ag in the non-variceal patients. In addition, there was a direct positive correlation between increased plasma VWF-Ag and the degree of oesophageal varices. Conclusion Since the plasma VWF-Ag level correlates with the presence and degree of OVs, it can be used as a noninvasive indicator of the presence and degree of OVs, However, further studies using larger sample might be needed to support this.

scholarly journals Autosomal recessive inherited bleeding disorders in Pakistan: a cross-sectional study from selected regions

2017 ◽  
Vol 12 (1) ◽  
Author(s):  
Arshi Naz ◽  
Muhammad Younus Jamal ◽  
Samina Amanat ◽  
Ikram Din ujjan ◽  
Akber Najmuddin ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Cross Sectional Study ◽  
Bleeding Disorders ◽  
Sectional Study ◽  
Cross Sectional

Determinants of bleeding phenotype in adult patients with moderate or severe von Willebrand disease

2012 ◽  
Vol 108 (10) ◽  
pp. 683-692 ◽  
Author(s):  
Eva M. de Wee ◽  
Yvonne V. Sanders ◽  
Eveline P. Mauser-Bunschoten ◽  
Johanna G. van der Bom ◽  
Manon E. L. Degenaar-Dujardin ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Cross Sectional Study ◽  
Von Willebrand Disease ◽  
Sectional Study ◽  
Cross Sectional ◽  
Bleeding Score ◽  
Type 3 ◽  
Von Willebrand ◽  
Unselected Cohort

SummaryWe performed a nation-wide cross-sectional study to evaluate determinants of bleeding symptoms in a large unselected cohort of adults with von Willebrand disease (VWD). VWD patients were included (n=664), based on lowest historically measured VWF:Ag and VWF:Act levels ≤30 U/dl. Menorrhagia (85%), cutaneous bleeding (77%), bleeding from minor wounds (77%) and oral-cavity bleeding (62%) occurred most frequently. Higher age was associated with a higher bleeding score (BS), determined according to Tosetto, in females. A 10 year increase in age was associated with 0.8 point (95% confidence interval [CI] 0.4–1.1) higher BS. Females had higher BS than males (median 12 vs. 10, p=0.012). BS differed significantly between VWD type 1, 2 and 3: median 9 (-2–31), 13 (-1–33) and 19.5 (1–35), respectively (p<0.001). BS was strongly associated with VWF and FVIII levels: individuals with VWF:Ag levels ≤10 IU/dl, VWF:Act ≤10 IU/dl and FVIII:C ≤10 IU/dl had, respectively, 5.3 point (95%CI 3.2–7.3), 4.3 point (95%CI 2.9–5.8) and 9.6 point (95%CI 6.5–12.7) higher BS, than those with levels >30 IU/dl. In type 3 patients 1 IU/dl FVIII:C decrease was associated with 0.6 point (95% CI 0.1–1.1) BS increase (p=0.021). In conclusion, in VWD patients the bleeding phenotype is strongly associated with type of VWD and VWF and FVIII levels.

scholarly journals Bleeding symptoms in patients diagnosed as type 3 von Willebrand disease: Results from 3WINTERS‐IPS, an international and collaborative cross‐sectional study

2020 ◽  
Vol 18 (9) ◽  
pp. 2145-2154 ◽  
Author(s):  
Alberto Tosetto ◽  
Zahra Badiee ◽  
Mohammad‐Reza Baghaipour ◽  
Luciano Baronciani ◽  
Javier Battle ◽  
...  
Keyword(s):  
Cross Sectional Study ◽  
Von Willebrand Disease ◽  
Collaborative Cross ◽  
Sectional Study ◽  
Cross Sectional ◽  
Type 3 ◽  
Von Willebrand

scholarly journals Type 3 VWD and an inhibitor to VWF: Challenges in diagnosis

2016 ◽  
Vol 3 (2) ◽  
pp. 1-3 ◽  
Author(s):  
S. Jenkins ◽  
Manuel Carcao ◽  
Vanessa Bouskill
Keyword(s):  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Bleeding Disorders ◽  
Limited Experience ◽  
Recurrent Epistaxis ◽  
History Of ◽  
Factor Concentrate ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Developing an inhibitor to von Willebrand factor (VWF) is extremely uncommon. Consequently, patients with von Willebrand disease (VWD) tend not to be routinely evaluated for inhibitors, leading to the possibility of delay in inhibitor diagnosis. We present such an occurrence to raise awareness, with a view to avoiding such delays. A 1-year-old male with no family history of bleeding disorders or parental consanguinity presented with a tongue bleed lasting three days. Investigations confirmed a diagnosis of Type 3 VWD. Over the next few months, the patient received seven exposures to Humate-P (a plasma derived FVIII containing von Willebrand factor concentrate), but developed an anaphylactic reaction necessitating adrenalin and Benadryl (diphenhydramine). The reaction quickly abated and did not recur with further exposure to Humate-P. In 2013, due to recurrent epistaxis and tonsillar bleeding, the patient was commenced on prophylaxis receiving Humate-P 50 RCo U/kg twice weekly. Despite this regimen, he continued to experience recurrent epistaxis, leading to escalation of prophylaxis to 3/week. In November 2014, he showed persistent tonsillar bleeding, despite having received two doses of Humate-P (each 40 RCo U/kg) in the previous 12 hours. Testing revealed reduced VWF:Ag, VWF:RCo and FVIII:C recoveries. Further testing revealed an anti-VWF antibody (2.6 BU) of unspecified Ig type. Since diagnosis of the inhibitor, he has received 100 RCo U/kg daily for prophylaxis and immune tolerance. He is now bleed-free; however, monthly inhibitor testing shows that his inhibitor persists. Given the limited experience and literature on inhibitors in VWD, the prognosis for such cases is unknown.

scholarly journals Inherited Bleeding Disorders in Iraq and Consanguineous Marriage

2018 ◽  
Author(s):  
Nidal Karim Al-Rahal
Keyword(s):  
Family History ◽  
Autosomal Recessive ◽  
Consanguineous Marriage ◽  
Von Willebrand Disease ◽  
Clotting Factor ◽  
Bleeding Disorders ◽  
Clotting Factors ◽  
Female Ratio ◽  
Increased Risk ◽  
Von Willebrand

Background: Consanguineous marriage is defined as inbreeding between second cousins or closer. In such families there will be a potential increase in the autosomal recessive traits with its lethal effect, with an increased risk of morbidity and mortality in the new generation.  Inherited bleeding disorders (InBDs) are rare complicated diseases, difficult and expensive to treat, the defect usually due to quantitative or qualitative deficiency of clotting factors, platelets or fibrinolysis. This study attempts to assess the diversity, the frequency and the clinical features of inherited bleeding disorders (InBDs) in central part of Iraq and to determine the state of consanguineous marriage. Materials and Methods: This is a prospective cross-sectional study conducted in the National Center of Hematology NCH, Baghdad, Iraq between June2014 and June 2017. In total, 256 pediatrics and adult patients were included. Full bleeding history, family history, drug history and consanguineous marriage were recorded and followed by medical examination.  First-line laboratory tests were performed and then were followed by further tests included mixing study, lupus anticoagulant testing, clotting factor activity assay, von Willebrand Antigen (VW: Ag), Ristocetin co factor vWF: RiCoF activity and platelet function test. Results: The range of age was from 1 month to 57 years, with mean age 8.424±8.623 years and median age of 6.5years. The male to female ratio was 1.1:1. The most common age group was in the range of 1-10 years (46.45%). Family history was positive in 55.07% of patients (P >0.05). The consanguinity was found in 76.95% of the families studied (P <0.0001).  The most prevalent InBD was von Willebrand disease (42.98%) with majority type 3VWD (86.4%). The second most prevalent was thrombasthenia (36.71%) and the majority had Glanzmann’s thrombosthenia (86.2%). Rare bleeding disorders (RBDs) were observed in 6.25% of patients and the most common factor deficiency was FVII.  Conclusion: Consanguinity is high in patients with inherited bleeding disorders in Iraq, leading to emergence of life-threatening autosomal recessive inherited diseases. Genetic counselling is recommended besides education and awareness to minimize such rare illnesses in the community.

Tonsillectomy in a Patient with Type 3 Von Willebrand Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5067-5067
Author(s):  
Emily K. Rimmer ◽  
Dawn Zawadski ◽  
Tracy Voth ◽  
Michael Gousseau ◽  
Donald S Houston
Keyword(s):  
Tranexamic Acid ◽  
Von Willebrand Factor ◽  
Fibrin Sealant ◽  
Von Willebrand Disease ◽  
Activity Level ◽  
Bleeding Disorders ◽  
Estimated Blood Loss ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Introduction: Type 3 Von Willebrand Disease (VWD) is a rare autosomal recessive bleeding disorder characterized by a complete deficiency of von Willebrand factor (VWF) and markedly reduced levels of FVIII, which confers a severe bleeding phenotype. Conventional management is with plasma-derived von Willebrand factor / FVIII concentrates. These products do not fully correct the bleeding diathesis, for several possible reasons: (a) platelets remain deficient in VWF; (b) subendothelial matrix remains deficient in VWF; and (c) available products lack the highest molecular weight VWF multimers. Because of the low prevalence of type 3 VWD, reports on surgical procedures are scarce. We reviewed the literature and identified one case report of a patient with type 3 VWD who underwent tonsillectomy (Alusi et al. 1995). That case was complicated by major intra-operative bleeding as well as prolonged hemorrhage in the two weeks following surgery, despite factor replacement with concentrate, cryoprecipitate, platelet transfusion and tranexamic acid. We report on the management of a patient with type 3 VWD undergoing a tonsillectomy, which demonstrates the importance of local measures in hemostatic control. Case: A 29 year old woman with Type 3 VWD (baseline VWF:Ag 4 IU/dL, VWF:RCoF <5 IU/dL, FVIII 1 IU/dL) had a 2 year history of recurrent tonsillar hemorrhage despite regular prophylaxis with plasma-derived VWF concentrate (Humate-P®). Each episode occurred in the absence of trauma or infection, and bleeding was difficult to control despite Humate-P and tranexamic acid. Lee et al. (2010) have previously reported that VWD is a cause of spontaneous tonsillar hemorrhage. Due to the recurrent nature of the bleeding episodes, a tonsillectomy was recommended. In preparation for the surgical procedure, we performed pharmacokinetic studies, which revealed a yield of VWF activity of 2.35IU/dL per U/kg and a half-life of VWF activity of 8.8 hours. We administered an initial loading dose of 63IU/kg (RCoF) of Humate-P preoperatively, achieving a VWF activity level (by latex agglutination: HemosIL vWF activity, Instrumentation Laboratories) of 126%. The tonsillectomy was uneventful, and the estimated blood loss intra-operatively was <50 mL. Surgical hemostasis was augmented by administration of tranexamic acid 1000mg intravenously pre-operatively and by continuous infusion intra-operatively, as well as 5 mL of fibrin sealant (Tisseel) administered to each tonsillar bed. A dose of Humate-P of 22.6 IU/kg was given post-operatively, and subsequent doses of 11.3 IU/kg were given q 4 hourly to maintain trough VWF activity of approximately 100IU/dL. Post-operative doses of tranexamic acid were omitted due to a transcribing error until day #3. On day #4 the Humate P dosing was reduced to 11.5U/kg q6h, which maintained trough VWF activity levels of approximately 50%. No bleeding occurred until post-operative day #9, when the eschar at the wound side detached. Bleeding continued despite re-bolus of Humate-P (23IU/kg) followed by resumption of q4h dosing, administration of tranexamic acid topically in the form of a 5% solution in addition to systemic administration, and application of topical silver nitrate. Hypotension transiently developed and the hemoglobin fell from 106 to 66g/L, requiring a return to the operating room. Further application of fibrin sealant promptly secured hemostasis. Conclusion: Surgery in a patient with type 3 VWD requires careful planning and collaboration between hematologists with expertise in bleeding disorders, the bleeding disorders nursing staff and surgical team. This case highlights the importance of monitoring for an extended period post-operatively, and demonstrates that bleeding can occur despite maintaining adequate VWF levels. Topical measures such as fibrin sealant play a key role in controlling bleeding in this context. Disclosures No relevant conflicts of interest to declare.

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