Rare bleeding disorders: spectrum of disease and clinical manifestations in the Pakistani population

Background@#Rare inherited coagulation factor deficiencies constitute an important group of bleeding disorders. A higher frequency of these disorders is seen in areas of high consanguinity.Our aim was to study the prevalence and spectrum of rare inherited bleeding disorders, characterize the severity of the deficiencies, identify different clinical manifestations, and evaluate different treatments provided. @*Methods@#This cross-sectional study was conducted in the Department of Haematology, Armed Forces Institute of Pathology Rawalpindi, between January 2014 and December 2018.A detailed history was taken, and an examination was performed. The signs and symptoms were noted, and the patients were diagnosed on the basis of a coagulation profile. The disease severity was assessed using factor assays. @*Results@#Among 2,516 patients with suspected coagulation disorders, 774 (30.8%) had an inherited bleeding disorder. Of the 774 patients, 165 (21.3%) had a rare bleeding disorder;91 (55.2%) of them were males, and 74 (44.9%) were females, with a male-to-female ratio of 1.2:1. The median patient age was 9 years 3 months. The most common disorder was factor VII deficiency (46 patients, 27.9%). The most common clinical presentation was bruising in 102 (61.8%) and gum bleeding in 91 (55.2%) patients. @*Conclusion@#The most common rare bleeding disorder in our population is factor VII deficiency. The prevalence of these bleeding disorders is high in our population due to a high number of consanguineous marriages.

Clinicohematological parameters and outcomes in a cohort of chronic lymphocytic leukemia patients with Deletion 17p from Pakistan

BACKGROUND: Chronic lymphocytic leukemia (CLL) exhibits profound heterogeneity in its clinical course. Its clinicohematological and cytogenetic features play a significant role in determining the clinical course and in predicting the treatment response and prognosis. In this context, 17p deletion is known to predict a poor prognosis, as these cases are refractory to conventional therapy. This study aimed to evaluate the clinicohematological characteristics, outcomes, and prognostic factors among CLL patients with and without del 17p in Pakistan. METHODS: This prospective observational study was conducted at the Department of Haematology, Armed Forces Institute of Pathology (Rawalpindi, Pakistan) between January 2013 and December 2017. Patients were diagnosed based on the International Workshop on Chronic Lymphocytic Leukaemia IWCLL criteria, their clinicohematological parameters were recorded, and cytogenetic analyses were performed. The time from diagnosis to treatment and the 2-year overall survival rate were also evaluated. RESULTS: We evaluated 130 CLL cases, including 24 patients (18.5%) with del 17p, who included 18 men (75%) and 6 women (25%). The median age was 68 years. Binet stage C was detected at the presentation in 16 patients (67%). Treatment was administered to 14 patients (70%) at a median interval of 11 months (range, 0–28 mo) after diagnosis. The overall response rate was 64.3%, the median event-free survival was 9 months (range, 1–23 mo), and the 2-year overall survival rate was 65%. CONCLUSION: Del 17p is relatively common in Pakistan, and patients harboring this deletion had poor treatment response and survival outcomes.

Hashimoto's thyroiditis: not uncommon in simple benign goiter. A review of 1102 thyroidectomies for simple benign goiter

Objective: To see the frequency of Hashimotos Thyroiditis [HT] in patients operated with the diagnosis of simple goiter

Study Design: A retrospective multicenter study

Place and duration: From 1[st] January 1999 to 31[st] March 2011 at three tertiary care hospitals

Methodology: All patients with simple benign goiter irrespective of age and sex are included in the study. Patients already diagnosed for hashimotos thyroiditis, recurrent goiter, abnormal thyroid hormone profile, diagnosed congenital thyroid pathology or non availability of postoperative histopathology were excluded from the study. Histopathology of all patients reviewed to see the frequency of hashimotos thyroiditis in patients operated for benign simple goiter

Results: Among a total of 1102 patients, 91.28% [n=1006] were female and the majority were in 5[th] decade [35.48%, n=391] of life. Histopathology review of all patients operated for benign simple goiter showed that 2.81% [n=31] were having Hashimoto's thyroiditis and majority [87.09%, n=27] were female. Hashimoto's thyroiditis were common in patients who was in the 3[rd] decade of life followed by 4[th] decade, i.e. 35.48% [n=11] and 32.26% [n=10] respectively

Conclusion: Hashimotos thyroiditis is not uncommon and due to its varied clinical presentation it should be ruled out in simple benign goiter before surgery

Early diagnosis of dengue virus infection in clinically suspected cases

Objective: Comparison of real time reverse transcriptase polymerase chain reaction [RTPCR] and immunoglobulin M [IgM] capture enzyme linked immunosorbent assay [ELISA] for diagnosis of dengue virus infection in first week of illness in clinically suspected patients of dengue fever

Study Design: Cross sectional study

Place and Duration of Study: Department of haematology, Armed Forces Institute of Pathology [AFIP] Rawalpindi from Jan 2013 to Nov 2013

Material and Methods: A cross sectional study including 68 clinically suspected patients of dengue fever according to the World Health Organization [WHO] criteria. IgM capture ELISA and RT PCR for dengue virus ribonucleic acid [RNA] was performed on samples collected from patients having fever for 1 to 7 days. These were divided into two groups. Patients in group 1 presented with fever of 4 days or less, patients in group 2 had fever of 5 to 7 days duration

Results: In group 1, 72% of the patients were positive by RT PCR while 31% were positive by IgM capture ELISA. In group 2, 43% of the patients were positive by RT PCR while 97% were positive by ELISA

Conclusion: RT PCR can be used for early detection of dengue virus infection in the first few days of fever while IgM ELISA is diagnostic afterwards

High prevalence of protein C, protein S, antithrombin deficiency, and factor V Leiden mutation as a cause of hereditary thrombophilia in patients of venous thromboembolism and cerebrovascular accident

To determine the frequency of Protein C, Protein S [PC and PS], antithrombin deficiency [AT III] and Factor V Leiden mutation [FVL] as a cause of thrombophilia in the patients with venous thromboembolism [VTE] and cerebrovascular accident [CVA]. It was an observational study conducted at Department of Haematology, Armed Forces Institute of Pathology [AFIP], Rawalpindi, Pakistan. All patients referred for thrombophilia screening from July 2009 to June 2012 were screened. Patients with evidence of VTE or CVA were screened for PC and PS, AT III deficiency, and FVL. Total 404 patients of age between 1-71 years mean 33 +/- 14 with male to female ratio of 2.4:1 had evidence of thrombophilia. Two hundred eighteen [54%] patients presented with CVA, 116 [29%] with deep vein thrombosis [DVT], 42 [10.5%] with pulmonary embolism [PE], and 28 [7.5%] with portal or mesenteric vein thrombosis [PV]. Protein C and S deficiency was detected in 35/404 [8.7%], AT III in 9/404 [2%], and FVL in 25/173 patients [14.5%]. The findings were suggestive of a significant association of FVL mutation for developing DVT [OR=11.0, 95% C I 4.6-26.3], CVA [OR=5.7, 95% C I 2.1-15.1], and PV [OR=5.4, 95% C I 1.3-21.9]. PC and PS deficiency was a significant risk factor for developing PE [OR=3, 95% C I 0.8-11.4]. FVL mutation and Protein C and S are the leading causes of thrombophilia with strong association of Factor V Leiden mutation as risk for developing DVT

Giant goiter: not uncommon in endemic areas of Pakistan. a 10 years experience

Objectives: To determine the prevalence of giant goiter and morbidity after surgery and to compare the data with the national and international literature

Study Design: A prospective, observational study

Place And Duration: Department of Surgery, Fauji Foundation Hospital, Rawalpindi from May 1999 to April 2008

Methodology: All patients with giant multinodular goiter [Grade IV] were operated and prevalence of compilations was recorded meticulously, and data compared with national and international literature

Results: A total of 744 patients operated and majority were female 94.89% [n=706] from 5[th] decade of life i.e. 35.75% [n=266]. Giant multinodular goiter [Grade IV] found in 26.08% [n=194]. Among them, 96.90% [n=188] were euthyroid. Near total thyroidectomy was done in 59.79% [n=116] patients, total thyroidectomy in 28.86% [n=56] and subtotal thyroidectomy in 11.35% [n=22] patients. Transient hypocalcaemia was the commonest complication observed, in 8.24% [n=16] patients followed by seroma formation- 7.21%, [n=14]. Permanent hopoparathyroidism-2.66%, [n=4], Permanent recurrent laryngeal nerve injury-1.03%, [n=2], transient recurrent laryngeal nerve palsy-4.63%, [n=9], postoperative bleeding-1.03%, [n=2] and wound infection noticed in 2.57% [n=5] patients

Conclusion: Giant goiter is not uncommon in our setup, with expected high postoperative complications so surgery should be done by experienced hands in the centers where all facilities are available. Public awareness should be created by health authorities and organizations regarding prevention and early treatment

Comparison of real time polymerase chain reaction with microscopy and antigen detection assay for the diagnosis of malaria

To determine the sensitivity of a real time polymerase chain reaction [PCR] for malaria diagnosis and to compare its accuracy with microscopy and an antigen based rapid diagnostic test [OptiMal]. Cross-sectional analytical study. Military Hospital, Armed Forces Institute of Transfusion and Armed Forces Institute of Pathology, Rawalpindi, from July to December 2011. Venous blood samples of 300 clinically suspected patients of malaria were tested for malaria parasite by microscopy and OptiMal; and malaria parasite index was calculated for the positive samples. Plasmodium genus specific real time PCR was performed on all specimens, targeting small subunit rRNA gene. Diagnostic accuracy of three tests was compared and cost analysis was done. Out of 300 patients, malaria parasite was detected in 110, 106 and 123 patients by microscopy, OptiMAL and PCR respectively. Real time PCR was 100% sensitive while microscopy and OptiMal had sensitivity of 89.4% and 86.2% respectively. All methods were 100% specific. The cost per test was calculated to be 0.2, 2.75 and 3.30 US$ by microscopy, OptiMal and PCR respectively, excluding the once capital cost on PCR equipment. Genus specific real time PCR for the diagnosis of malaria was successfully established as a highly sensitive and affordable technology that should be incorporated in the diagnostic algorithm in this country.

Frequency of abo and RH [D] blood groups among blood donors in Rawalpindi/Islamabad area

To determine the frequency of various ABO and Rh [D] blood groups among the blood donors in Rawalpindi/Islamabad area of Pakistan. Cross sectional descriptive study. Armed Forces Institute of Transfusion [AFIT], Rawalpindi from Sep 2010 to Jan 2011. A total of 4642 healthy adult, blood donors [volunteer and directed both] belonging to Rawalpindi/Islamabad region were included. From each donor 2 ml of EDTA blood was taken. ABO and Rh [D] blood grouping were carried out by tube method using commercially prepared antisera. The frequency of each type was calculated. Among ABO blood groups the most frequent was B with 1593 subjects [34.3%], followed by O with 1454 [31.3%], A with 1124 [24.2%], and AB with 471 [10.1%] individuals. The Rh [D] positive were 4226 subjects [91%] and Rh [D] negative were 416 [9%]. Among Rh [D] positive cases, blood group B was most frequent with 1476 [34.9%] individuals, however among Rh [D] negative individuals the most frequent blood group was O with 149 individuals [35.8%]. 'B' was most frequent among the ABO blood groups. Knowledge of prevalence of various blood groups in the area will help in managing the transfusion services

Platelet count in malaria

To evaluate the significance of platelet count in cases of malaria at presentation. Descriptive study. Department of pathology CMH Lahore, from Aug 2007 to Sep 2008. A total of 256 patients of all ages with short history of febrile illness, rigors and chills were included in the study. Three ml blood sample was taken to prepare thick and thin blood smears. The smears were stained with Leishman's stain and examined'for malarial parasite. Complete blood counts of all the subjects were carried out with Sysmex KX -21 hematology analyzer. Out of 256 patients, 102 [40%] were positive for malaria on microscopy. 80 [31%] had Plasmodium vivax and 22 [9%] had Plasmodium falciparum infection. Thrombocytopenia was found in 66 [82.5%] and 19 [86.45%] patients of Plasmodium vivax and plasmodium falciparum respectively. Thrombocytopenia is a frequent finding in cases of malaria at presentation. Its presence in a patient with acute febrile illness increases the probability of malaria. Replacement therapy is usually not required and platelet count becomes normal after anti malarial treatment