scholarly journals Mild bleeders: Diagnosis is elusive in large number of patients

Author(s):  
Mrinalini Kotru ◽  
Deepti Mutereja ◽  
Abhishek Purohit ◽  
Seema Tyagi ◽  
Manoranjan Mahapatra ◽  
...  

Abstract. Background: Bleeding is a common clinical presentation. Even patients with mild bleeding disorders are extensively investigated for ascertaining the cause. The present study was conducted in order to evaluate the extent of the possibility of diagnosis in mild bleeding disorders.Material and Methods: This was a prospective study of patients referred for work up of mild bleeding for a period of 13 months. A complete blood count, peripheral smear examination, Prothrombin time, Partial Thromboplastin time and Thrombin Time, Platelet Aggregometry test, tests for von Willebrand’s disease and Platelet function 3 availability were measured. Results: 164 patients presented with mild bleeding, in 114 of the  patients a single site of bleeding was present. Epistaxis was the most common presentation (39%). Cutaneous bleeding (petechiae and purpura) was the next common site. History of a major bleeding tendency in the family was present only in 11 patients. The investigations showed that VWD (17/164), followed by clotting disorders (CD) mainly mild hemophilia (15/164) were the most common diagnosable cause. There were also 4 cases of hypofibrinogenemia. The disorders of platelets (Platelet function defects/PFD) were the least common (9/164). Rest 123 (75%) patients could not be diagnosed on the basis of these investigations and were labeled as  Bleeding disorders – Unclassified (BDC). Conclusion: n our study, 75% of the patients with mild bleeding remained undiagnosed even after extensive laboratory workup, thus raising a very pertinent question that is it necessary that all mild bleeders submit to a broad battery of investigations, as the diagnosis continues to be elusive despite extensive workup.

Author(s):  
Surendra Kumar ◽  
Rajkumar Lakhiwal ◽  
Vinod Aswal ◽  
Suresh Gajraj ◽  
Ishan Patel ◽  
...  

Background: Dengue is a major international health concern that is prevalent in tropical and sub-tropical countries. It is 2nd most common arthropod borne disease in India. There are certain clinical features that are associated with Dengue in addition of the classical features. Previously organ impairment has been only considered under set up of severe disease. On the recent years, several studies have suggested the possibility of early involvement of the liver in dengue. Further due to its atypical presentation often dengue missed out as a differential diagnosis.Methods: A total of 50 patients were selected to be a part of study after applying inclusion and exclusion criteria. Only those patients were included in the study who had classical features of dengue- fever with chills, body ache, headache, rash, bleeding manifestations and thrombocytopenia and had a positive ELISA test i.e. IgM antibodies against dengue virus. Patients who had malaria and enteric fever were excluded from the study. All patients were subjected to a detailed history and a thorough clinical examination. A complete blood count, liver function tests, renal function tests, chest X-ray and USG abdomen were also done.Results: An analysis of 50 patients suffering from dengue showed liver dysfunction was present in all patients. Vomiting was an important symptom present upto 70% of patients. SGOT levels were higher than SGPT levels. Hepatosplenomegaly and ascitis were also present in significant number of patients. An analysis of these patients revealed that patients typically demonstrate high grade fever, body ache, rash, thrombocytopenia and bleeding tendency, there were other features such as liver dysfunction including a preferential rise of SGOT, hepatosplenomegaly, ascitis, pleural effusion and leucopoenia.Conclusions: This study showed that dengue fever was seen in the third decade and that AST and ALT levels were raised in the majority of these patients. It was also found that AST levels were more than ALT levels. So, AST and ALT can be a useful early marker to assess the severity of the disease which can thus lead to early recognition of high risk cases. The presence of raised liver enzymes in all patients, ascitis, hepatosplenomegaly, elevation of SGOT more than SGPT, should be kept in mind when evaluating patients with suspected dengue.


Author(s):  
Benazeer Mansuri ◽  
Komal P. Thekdi

Background: Pancytopenia is consequence of many haematological condition with an extensive differential diagnosis. A prompt intervention is required to avoid complications. The severity and the underlying pathology determines the management and prognosis. Present study was conducted to assess the etiology, clinical profile and bone marrow morphology of pancytopenia.Methods: A prospective study was carried out among 50 consecutive patients with pancytopenia. Blood samples of the patients were analyzed for complete blood count and peripheral smear along with presence and absence of immature cells and abnormal cells. In bone marrow examination, morphology of all cells lineage, cellularity, parasite and abnormal cells were scrutinized. Trephine biopsy was done if indicated. Special investigations were done to confirm the diagnosis.Results: Among the 50 cases studied, age of the patients ranged from 1 to 70 years with a slight male predominance. Most common age group 11-20 years. Most of the patients presented with generalized weakness and fever. The commonest physical finding was pallor, followed by splenomegaly and hepatomegaly. The commonest marrow finding was hyper cellularity with megaloblastic erythropoiesis. The commonest cause for pancytopenia was megaloblastic anemia.Conclusions: The present study concludes that hematological investigations along with other supportive tests are helpful to diagnose or to rule out the causes of pancytopenia. Megaloblastic anemia is commonest cause of pancytopenia in most Indian and subcontinent studies. Substantial number of patients had reversible etiology. Hence complete work up including clinical details with hematological examination along with bone marrow study will lead to early and proper diagnosis and management.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1239-1239
Author(s):  
Jayson M. Stoffman ◽  
Archibald Mcnicol ◽  
Teresa Zelinski ◽  
Bernard N. Chodirker ◽  
Sara J. Israels

Abstract Noonan syndrome (NS) is an autosomal dominant disorder characterized by variable expression of multiple defects including short stature, facial dysmorphias, congenital heart defects, developmental delay, and hematological abnormalities. A bleeding tendency has been variably described in patients with NS; Factor XI deficiency and platelet function abnormalities are reported most frequently. Recently, germline missense mutations in the PTPN11 gene have been identified in up to 50% of individuals with NS. PTPN11 encodes the ubiquitously expressed cell-signaling mediator SHP-2, a non-transmembrane protein tyrosine phosphatase involved in the normal activation of the Ras-MAPK signaling cascade. SHP-2 has a pivotal role in cell proliferation, differentiation, and survival, but also modulates platelet responses to some stimuli. Some PTPN11 mutations lead to altered SHP-2 phosphatase activity, and have been shown to impact cardiac development in a mouse model of NS. This study examined the potential association among PTPN11 mutations, platelet function abnormalities, and platelet SHP-2 activity in patients with NS. Eighteen patients with a clinical diagnosis of NS were studied: 14 (78%) were female and the mean age was 20.7 years (range 4–56 years). A validated bleeding questionnaire was administered to each participant, and platelet aggregometry was performed on platelet-rich plasma according to standard clinical practice. SHP-2 was isolated by immunoprecipitation from agoniststimulated platelets and phosphatase activity measured spectrophotometrically. PTPN11 mutations were identified by dHPLC and defined by DNA sequencing in each participant to characterize the presence and the precise nature of a mutation associated with their NS. Seven (39%) participants were classified as bleeders on the basis of the questionnaire; of these, four had no hemostasis abnormality identified. One participant had mild Factor XI deficiency. Seven participants had abnormalities of platelet aggregation, and four participants had decreased platelet dense granule numbers and ATP release. PTPN11 mutations were identified in 12 (67%) participants: seven were the commonly described mutation in Exon 8; four members of a three-generation family had a previously described Exon 3 mutation; and one individual had a mutation in Exon 12 which is usually associated with LEOPARD syndrome. Mutations in other genes associated with NS were not evaluated in this study. Six patients with PTPN11 mutations were clinically classified as bleeders, but no correlation was found between PTPN11 mutation and agonist-induced platelet aggregation or SHP-2 phosphatase activity. Three patients with platelet function abnormalities had no PTPN11 mutation identified. Not all patients with NS have a clinical bleeding profile or platelet function abnormalities. Neither clinical bleeding history nor platelet function abnormalities correlated with PTPN11 mutations, suggesting that additional factors may be required for a bleeding phenotype associated with PTPN11 mutations. Mutations in other NS-associated genes may contribute to a bleeding phenotype. Abnormalities in platelet aggregometry could not be explained on the basis of SHP-2 activity, although it is possible that changes in enzyme activity downstream in the Ras-MAPK pathway may impact platelet function in some patients with NS. Ultimately, the identification of a molecular basis for the frequently observed platelet aggregation defects could provide a means to predict the risk of bleeding in patients with NS.


2014 ◽  
Vol 34 (S 01) ◽  
pp. S53-S56
Author(s):  
J. Lohse ◽  
J. Stächele ◽  
A. Heilmann ◽  
F. Schwier ◽  
U. Schmidt ◽  
...  

SummarySummary: The manifestation of an unclear bleeding tendency in childhood calls for an extended coagulation work-up, particularly when a battered child syndrome is suspected and typical concomitant injuries are absent. The chosen diagnostic tests should be able to detect the presence of relatively common coagulation defects such as von Willebrand syndrome or hemophilia, but also rare diseases such as inherited thrombocytopathies. The PFA-100® test does not help to provide a definite diagnosis especially in cases of mild inherited thrombocytopathies, since in most cases the PFA-100® test results are normal. For this purpose, specific platelet function testing is needed. However, the methods are only available in some coagulation laboratories. Also, other limitations need to be taken into consideration such as pre-analytical problems and difficulties in the interpretation of test results especially in infants.We present two cases that were diagnosed with an aspirin-like defect as an inherited thrombocytopathy, even though their PFA-100 closure times were within the normal range. Based on pathological findings in the platelet aggregometry test, this diagnosis could be made.


2011 ◽  
Vol 17 (6) ◽  
pp. E131-E137 ◽  
Author(s):  
Munira Borhany ◽  
Tahir Shamsi ◽  
Arshi Naz ◽  
Asif Khan ◽  
Kousar Parveen ◽  
...  

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.


Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 85-91
Author(s):  
Kristi J. Smock ◽  
Karen A. Moser

Abstract Bleeding disorders with normal, borderline, or nondiagnostic coagulation tests represent a diagnostic challenge. Disorders of primary hemostasis can be further evaluated by additional platelet function testing modalities, platelet electron microscopy, repeat von Willebrand disease testing, and specialized von Willebrand factor testing beyond the usual initial panel. Secondary hemostasis is further evaluated by coagulation factor assays, and factor XIII assays are used to diagnose disorders of fibrin clot stabilization. Fibrinolytic disorders are particularly difficult to diagnose with current testing options. A significant number of patients remain unclassified after thorough testing; most unclassified patients have a clinically mild bleeding phenotype, and many may have undiagnosed platelet function disorders. High-throughput genetic testing using large gene panels for bleeding disorders may allow diagnosis of a larger number of these patients in the future, but more study is needed. A logical laboratory workup in the context of the clinical setting and with a high level of expertise regarding test interpretation and limitations facilitates a diagnosis for as many patients as possible.


2021 ◽  
Vol 11 (2) ◽  
pp. 151-155
Author(s):  
Twasol Elsheikh Musa Altayeb ◽  
Nasreldeen Ali Mohammed ◽  
Sara Abdelghani ◽  
Lienda Bashier Eltayeb

The aim of this study was to assess visceral leishmaniasis (VL) among infected Sudanese patients in Al–Gedaref state. Methods and Results: A case-control study was conducted among patients with VL attending Al–Gaderif Teaching Hospital. A total of 80 subjects were included in the study: 40 patients with VL (the main group [MG]) and 40 apparently healthy individuals (the control group [CG]). The complete blood count (CBC) was determined using the Sysmex KX-21 N hematological analyzer. The platelet-poor plasma was used to determine prothrombin time (PT), thrombin time (TT), and activated partial thromboplastin time (aPTT). The age group of 12-21 years was the most frequent (40%) among VL patients. Male patients were significantly more frequent (72.5%) than females (P-value=0.02). In MG, the Hb level was 8.71±1.73g/dL, compared to 14.25±4.11g/dL in CG, which reflected the severity of the disease. WBCs and neutrophils decreased significantly, compared to CG, but lymphocytes increased significantly. Thrombocytopenia was observed among pediatric patients, indicating bleeding tendency as one of the VL complications. The platelet and coagulation profile of patients was also altered. PT and aPTT were prolonged significantly, compared to CG.


1999 ◽  
Vol 19 (04) ◽  
pp. 168-175 ◽  
Author(s):  
M. Weippert-Kretschmer ◽  
V. Kretschmer

SummaryPerioperative bleeding complications due to disorders of primary haemostasis are often underestimated. Routine determination of primary haemostasis is still problematic. The in vivo bleeding time (BT) shows low sensitivity and high variability. In this contribution the results and experiences with the IVBT having been obtained in various studies and during 10 years of routine use are reported. Patients and Methods: Blood donors before and after ASA ingestion, patients with thrombocytopenia as well as congenital and acquired platelet function disorders. Monitoring of desmopressin efficacy. IVBT with Thrombostat 4000 (tests with CaCl2 = TST-CaCl2 and ADP = TST-ADP) and PFA-100 (test cartridges with epinephrine = PFA-EPI and ADP = PFA-ADP). Results and Conclusions: IVBT becomes abnormal with platelet counts <100,000/μl. With platelet counts <50,000/μl the results are mostly outside the methodical range. IVBT proved clearly superior to BT in von Willebrand syndrome (vWS). All 16 patients with vWS were detected by PFA-EPI, whereas with BT 7 of 10 patients with moderate and 1 of 6 patients with mild forms of vWS were spotted. The majority of acquired and congenital platelet function disorders with relevant bleeding tendency were detectable by IVBT. Sometimes diagnostic problems arose in case of storage pool defect. Four to 12 h after ingestion of a single dose of 100 mg ASA the TST-CaCl2 became abnormal in all cases, the PFA-EPI only in 80%. However, the ASA sensitivity of TST-CaCl2 proved even too high when looking for perioperative bleeding complications in an urological study. Therefore, the lower ASS sensitivity of the PFA-100 seems to be rather advantageous for the estimation of a real bleeding risk. The good efficacy of desmopressin in the majority of cases with mild thrombocytopenia, congenital and acquired platelet function disorders and even ASS-induced platelet dysfunction could be proven by means of the IVBT. Thus IVBT may help to increase the reliability of the therapy. However, the IVBT with the PFA-100 is not yet fully developed. Nevertheless, routine use can be recommended when special methodical guidelines are followed.


Author(s):  
Antonio Girolami ◽  
Diana Noemi Garcia de Paoletti ◽  
Marcelo Leonardo Nenkies ◽  
Silvia Ferrari ◽  
Hugo Guglielmone

Background: Investigation of rare bleeding disorders in Latin-America. Objective: The report of a new case of FX deficiency due to a compound heterozygosis. Methods: Accepted clotting procedures were used. Sequencing of DNA was carried out by means of Applied Biosystems Instruments. Results: A compound heterozygote due to the association of a new mutation (Gla72Asp) with an already known mutation (Gly154Arg) of the FX gene is reported. The proposita is a 38 year old female who had a moderate bleeding tendency (menorrhagia, epistaxis, easy bruising). The proposita has never received substitution therapy but in the occasion of a uterine biopsy. The mother was asymptomatic but was a heterozygote for the new mutation. The father was asymptomatic but had deserted the family and could not be investigated. After this abandonment the mother of the proposita re-married with an asymptomatic man and she gave birth to a son who was asymptomatic but was also heterozygous for the new mutation (Gla72Asp). As a consequence it has to be assumed that the first husband of the mother of the proposita was heterozygous for the known mutation (Gly154Arg). Conclusion: This is the third case of a new mutation in the FX gene reported, during the past few years, in Argentina.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1417.1-1417
Author(s):  
M. Osipyan ◽  
M. Efraimidou ◽  
V. Vardanyan ◽  
K. Ginosyan

Background:Numerous joint disorders initially produce swelling in a single joint and new onset monoartritis will probably further lead to the involvement of other joint groups and development of extraarticular manifestations. It is essential to take a proper diagnostic approach for organizing appropriate treatment and lowering possibility of disease progression.Objectives:The aim of this study was to investigate joint distribution, determine rheumatological diseases of patients with acute monoarthritis and reveal the development of further systemic manifestations.Methods:100 patients (age 18-75 years) with clinically apparent monoarthritis of less than 6 weeks duration were included in the study. Criteria of exclusion were infection, trauma and crystal induced arthritis. Joint distribution, presence of systemic manifestations and development of chronic inflammatory rheumatic disease were evaluated. Presence of arthritis was proved with help of ultrasound examination. Complete blood count, ESR, CRP, RF, anti-CCP; HLAB27; MEFV mutations and X-ray of swollen joint were performed for all patients. Temperature was also measured.Results:Mean age of patients with acute monoarthritis was 46±13 years. Female predominance was noted (61%). 71% of patients had elevated ESR, 69%- CRP. In 24% of cases homozygous or heterozygous mutations of MEFV gene were revealed. 21% of patients had positive RF and 18% - anti-CCP. 11% patients carried HLA-B27 antigen. 28% of examined patients had subfebril fever. Hepatosplenomegaly was determined in 16%, uveitis in 5%, psoriatic plaque in 4%, interstitial pneumonia in 2% of casesAt the baseline 82 patients were diagnosed with rheumatologically disease. Baseline data is shown in the Table 1 bellow.Table 1.Baseline dataDiagnosis Number of patientsFMF23Osteoarthritis (reactive synovitis)16Rheumatoid arthritis15Reactive arthritis10Ankylosing spondylitis6Psoriatic arthritis4SLE3Schonleyn-Henoch purpura2Sarcoidosis2Behcet diseases1Conclusion:In this study monoarhtritis in majority of cases underlies FMF. Though FMF is not considered as a frequent cause of acute monoarthritis, more attention should be paid on this pathology in focus of monoarthritis, especially in specific for FMF region. Further follow up of acute monoarthritis progression is needed.References:[1]A. Becker, J. Daily, K. Pohlgeers. Acute Monoarthritis: Diagnosis in Adults.Am Fam Physician 2016; 94(10): 810-816[2]S. Camacho-Lovillo, A. García-Martínez. Arthritis as presentation of familial Mediterranean fever. An Pediatr (Barc). 2015; 83(2):130. DOI: 10.1016/j.anpede.2015.07.007[3]J. Ellis. Acute monoarthritis. JAAPA. 2019, 32(3):25-31. doi: 0.1097/01.JAA.0000553379.52389.ebDisclosure of Interests:None declared


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