Saqib Ansari

Use of recombinant activated factor VII for massive postpartum hemorrhage

Objective. We hypothesised that patients with massive postpartum hemorrhage (PPH), defined as blood loss >1,500 ml, may benefit from the use of activated recombinant factor VII (rFVIIa). Design. Retrospective cohort study. Setting. Department of Obstetrics & Gynaecology, Dow University of Health Sciences. Population. Thirty‐four women with a diagnosis of massive PPH. Methods. All patients with PPH who were admitted to the Department of Obstetrics & Gynecology and Surgical Intensive Care Unit of Civil Hospital Karachi, Pakistan, were included in the study. From March 2005 to October 2006, 34 patients fulfilled the criteria of massive PPH, of which 18 received rFVIIa to control bleeding, and 16 patients did not. Availability and cost of rFVIIa were the factors in drug allocation. Main outcome measures. Maternal mortality, correction of coagulopathy, the amount of blood products transfused and preservation of fertility. Results. Patients receiving rFVIIa had lower maternal mortality (5/18, 28% versus 8/16, 50%, OR: 0.04 (0.002, 0.83)), and received a lower number of packed red cell transfusions (4.0±4.46 versus 9.61±6.7, p value 0.007), against the comparison group. Patients receiving rFVIIa had lower activated partial thromboplastin (median: 13.0; 25–75th percentile: −25.0, −8.0, signed rank p<0.0001), and lower prothrombin times (median: −8.8; 25–75th percentile: −24.2, −4.8), after administration of drug. There was no significant difference in the rate of hysterectomy between the 2 groups (11/18 (61%) versus 6/16 (38%)). No adverse event attributable to rFVIIa was observed in the study. Conclusion. Activated recombinant factor VII can be a life‐saving drug in patients with massive PPH.

Bleeding disorders in the tribe: result of consanguineous in breeding

ObjectiveTo determine the frequency and clinical features of bleeding disorders in the tribe as a result of consanguineous marriages.DesignCross Sectional StudyIntroductionCountries in which consanguinity is a normal practice, these rare autosomal recessive disorders run in close families and tribes. Here we describe a family, living in village Ali Murad Chandio, District Badin, labeled as haemophilia.Patients & MethodsOur team visited the village & developed the pedigree of the whole extended family, up to seven generations. Performa was filled by incorporating patients, family history of bleeding, signs & symptoms, and bleeding from any site. From them 144 individuals were screened with CBC, bleeding time, platelet aggregation studies & RiCoF. While for PT, APTT, VWF assay and Factor VIII assay, samples were kept frozen at -70 degrees C until tested.ResultsThe family tree of the seven generations comprises of 533 individuals, 63 subjects died over a period of 20 years and 470 were alive. Out of all those 144 subjects were selected on the basis of the bleeding history. Among them 98(68.1%) were diagnosed to have a bleeding disorder; 44.9% patients were male and 55.1% patients were female. Median age of all the patients was 20.81, range (4 months- 80 yrs). The results of bleeding have shown that majority had gum bleeding, epistaxis and menorrhagia. Most common bleeding disorder was Von Willebrand disease and Platelet functional disorders.ConclusionConsanguineous marriages keep all the beneficial and adversely affecting recessive genes within the family; in homozygous states. These genes express themselves and result in life threatening diseases. Awareness, education & genetic counseling will be needed to prevent the spread of such common occurrence of these bleeding disorders in the community.

Efficacy of hydroxyurea in providing transfusion independence in β-thalassemia.

BackgroundPacked red blood cell (PRC) transfusion with iron chelation is the mainstay of treatment for &bgr;-thalassemia major. This prospective interventional trial serves as a follow up to our similar earlier study that evaluated the efficacy and safety of hydroxyurea (HU) in minimizing PRC transfusions in patients with &bgr;-thalassemia major. MethodsOne hundred fifty-two patients with &bgr;-thalassemia major received HU at a mean dose of 16 mg/kg/d. The results were analyzed at the end of 24 months. Transfusion requirement during the 6 months preceding the study was considered as the control. ResultsOne hundred forty-six of 152 patients were evaluated after 24 months of follow up; 6 patients were either lost to follow-up or withdrew consent. Grade 1 myelosuppression was observed in 4 patients and diarrhea in 2 patients. Sixty children (41%) did not require any transfusion after using HU; 57 patients (39%) showed partial response with greater than 50% reduction in PRC transfusion; and 29 patients (20%) were nonresponders with less than 50% reduction in PRC transfusion. The mean volume of PRC transfused was reduced for all patients. ConclusionsHU was found to be safe in patients with &bgr;-thalassemia major, and resulted in the reduction of transfusion requirement and in an increase in the interval between transfusions.

Molecular epidemiology of β-thalassemia in Pakistan: Far reaching implications

BACKGROUND: β -Thalassaemia, an autosomal recessive hemoglobinopathy, is one of the commonest genetically transmitted disorders throughout the world. Collective measures including carrier identification, genetic counseling and prenatal diagnosis are required for preventing β-thalassemia. Aim: To achieve this objective, Identification of the spectrum of genetic mutations, especially for various ethnic backgrounds in Pakistan. Therefore, we designed a cross sectional prospective study to identify the frequency of various gene mutations in different ethnic groups of Pakistan. MATERIALS AND METHODS: Over a 5-year period, DNA from 648 blood samples {including specimens of chorionic villus sampling (CVS)} were analyzed for the twelve most common β-thalassemia mutations found in the Pakistani population by a Multiplex amplification refractory mutation system (ARMS). Each sample was analyzed for the mutation as well as the normal gene, appropriate with negative and positive controls, and reagent blanks. RESULTS: Out of 648 samples mutations were identified in 640 (98.75%) samples by multiplex ARMS. 8 common β-thalassemia mutations were identified in 8 different ethnic groups accounting for 93.9% of the β-thalasemia alleles. CONCLUSIONS: Based on the outcome of this study a cost effective proposal is formulated for detection of β-thalassemia mutations.

Transfusion Transmitted Infections in Patients with Hemophilia of Karachi, Pakistan

The aim of the study was to assess the prevalence of HCV, HBV, and HIV infections among the patients with hemophilia. Patients with Hemophilia A and B were evaluated who visited hospital for factor replacement therapy. The viral markers tested in these patients included anti-HCV-Ab, HBsAg, and anti-HIV-Ab. Seroprevalence was compared from 5717 exchange healthy blood donors for same markers. A total of 173 multitransfused male hemophiliacs showed prevalence of 51.4% for HCV, 1.73% for HBV, and nil for HIV. In blood donors seroprevalence was 1.9% for HCV, 1.81% for HBV, while no HIV-positive case was detected. Prevalence of anti-HCV-Ab was significantly high in patients with hemophilia than normal donors (P = .0005). This study showed that HCV infection was more frequently identified than HBV and HIV infections in multitransfused hemophiliacs. The frequency of hepatitis C among blood donors is also higher than that of hepatitis B which is showing downward trend.

Camel collision as a major cause of low cervical spinal cord injury

One hundred and forty patients with low cervical spinal cord injuries, who were admitted to the Riyadh Armed Forces Hospital over the past 10 years were reviewed. Motor vehicle accidents constituted 119 (85%) of the patients. Camel collisions were a major cause of vehicle accidents 39 (33%), after rollover accidents 70 (59%), and much more than head on collisions 9 (7.5%). Male to female ratio was 14 : 1 with a mean age of 32 years. Camel collision although a commonly observed cause of motor vehicle accidents in the Middle East has not been mentioned in the literature before. The mechanism of injury is not much different, but the exact description of the accident and sustaining injury is interesting because it leads to localised damage to the neck without major body trauma and mortality.

Efficacy of hydroxyurea (HU) in reduction of pack red cell (PRC) transfusion requirement among children having beta-thalassemia major: Karachi HU trial (KHUT).

Background Packed red blood cell (PRC) transfusion with iron chelation is the mainstay of treatment for patients with beta-thalassemia major. Hemoglobin F augmentation is another approach to treat this hemoglobinopathy. This study evaluates the efficacy and safety of hydroxyurea (HU) in minimizing PRC transfusions in patients with beta-thalassemia major. Method Twenty-three patients with beta-thalassemia major received HU at a mean dose of 16 mg/kg/d. The results were analyzed at the end of 24 months. Transfusion requirement during the 6 months preceding the study was considered as the control. Result Twenty patients were evaluable after 24 months. The mean volume of PRC transfused was reduced from 2126.45 mL to 1489.59 mL (P<0.001). The interval between transfusions was increased by 68.7%. Grade I myelosuppression was observed in 4 patients and diarrhea in 2 patients. Conclusions HU was found to be safe in patients with beta-thalassemia major, and resulted in reduction in the transfusion requirements and in increase of the intervals between transfusions.

Gγ-Xmn I polymorphism: a significant determinant of β-thalassemia treatment without blood transfusion.

&bgr;-thalassemia is characterized by impaired &bgr;-chain synthesis leading to ineffective erythropoiesis, severe anemia, and a need for blood transfusion. Presence of Xmn I polymorphism (−158 C-T nucleotide change) in &ggr;-globin gene is associated with a higher fetal hemoglobin and a lesser clinical severity. This prospective study attempted to find out the effect of hydroxyurea (HU) on &bgr;-thalassemia patients in the presence or absence of Xmn I polymorphism. A total of 143 consecutive &bgr;-thalassemia patients received HU (16 mg/kg/d). Sixty-four (44.7%) had Xmn I polymorphism (either homozygous or heterozygous). Patients were evaluated at a median duration of 3 years (range, 6 mo to 9 y). Responders became transfusion independent after 6 months, partial responders had a least 50% reduction in transfusion requirement and nonresponders had no significant reduction. Of the 64 patients with Xmn I polymorphism, 44 (69%) showed response (P<0.01), whereas in those who lacked Xmn I polymorphism (n=79), only 17 (21%) were responders. This study showed that the presence of Xmn I polymorphism in &bgr;-thalassemia is a predictor of response to HU and highlights the possibility of managing this subset of patients without blood transfusion.

Congenital Bleeding Disorders in Karachi, Pakistan

Objective: To determine the frequency of inherited bleeding disorders, its complications, and treatment modalities available for its treatment. Design: Cross-sectional study. Patients and Methods: Patients with a history of bleeding tendency were tested for confirmation of the diagnosis. History and clinical findings were recorded. Laboratory analysis included prothrombin time (PT), activated partial thromboplastin time (APTT), bleeding time (BT), and fibrinogen assay. Patients with prolonged APTT were tested for factors VIII (FVIII) and IX (FIX). 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, FV, FX, and FII were tested. Platelet aggregation studies were done when there was isolated prolonged BT. Urea clot solubility test was done when all coagulation tests were normal. All patients with hemophilia A and B were evaluated for inhibitors. Results: Of the 376 patients, inherited bleeding disorder was diagnosed in 318 (85%) cases. Median age of patients was 16.4years. Hemophilia A was the commonest inherited bleeding disorder that was observed in 140 (37.2%) followed by vWD 68 (18.0%), platelet function disorders 48 (12.8%), and hemophilia B in 33 (8.8%) cases. We also found rare congenital factor deficiencies in 13 (3.4%), low VWF in 11 (3.0%) participants and 5 (1.3%) in female hemophilia carriers. Hemarthrosis was the most frequent symptom in hemophilia A and B (79.7%) involving knee joint. Inhibitor was detected in 21 (15%) cases. Fresh frozen plasma/cryoprecipitate were the most common modality of treatment. In 58 patients, no abnormality was detected in coagulation profile. Conclusion: Hemophilia A and vWD are the most common congenital bleeding disorders in this study. Hemarthrosis involving knee joint was the most common complication. Inhibitor was detected in a significant number of patients. Plasma is still the most common modality of treatment.

Clinical features and types of von Willebrand disease in Karachi.

This study was conducted on patients with a history of congenital bleeding disorders or with suspected bleeding tendencies. Laboratory analysis revealed Von Willebrand disease (VWD) in 68 (21.3%) of 318 participants with male to female ratio of 0.8: 1 (31 to 37) and median age 17 years (range 2-45 years). Type 3 being the most frequent, 35 (51.4%) of 68, type 2, 20 (29.4%) of 68, and lastly type 1, 13 (19.1%) of 68. A total of 55.8% patients with VWD presented with mucocutaneous bleeding. Menorrhagia was the most common presentation of female patients. Von Willebrand disease (21.3%) was the second common bleeding disorder and the most common coagulation defect among females with menorrhagia. However, the frequency in the study was quite low when compared to the western world. Similarly, low frequency of VWD type 1 might be due to the fact that only symptomatic patients visited us. Further studies are needed as there is limited information on VWD in the developing countries. This will help in the development of expertise for the accurate diagnosis & proper management.