scholarly journals Cryptogenic oozers and bruisers

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.

Author(s):  
Akbar Dorgalaleh ◽  
Yadolah Farshi ◽  
Kamand Haeri ◽  
Omid Baradarian Ghanbari ◽  
Abbas Ahmadi

AbstractIntracerebral hemorrhage (ICH) is the most dreaded complication, and the main cause of death, in patients with congenital bleeding disorders. ICH can occur in all congenital bleeding disorders, ranging from mild, like some platelet function disorders, to severe disorders such as hemophilia A, which can cause catastrophic hemorrhage. While extremely rare in mild bleeding disorders, ICH is common in severe coagulation factor (F) XIII deficiency. ICH can be spontaneous or trauma-related. Spontaneous ICH occurs more often in adults, while trauma-related ICH is more prevalent in children. Risk factors that can affect the occurrence of ICH include the type of bleeding disorder and its severity, genotype and genetic polymorphisms, type of delivery, and sports and other activities. Patients with hemophilia A; afibrinogenemia; FXIII, FX, and FVII deficiencies; and type 3 von Willebrand disease are more susceptible than those with mild platelet function disorders, FV, FXI, combined FV–FVIII deficiencies, and type 1 von Willebrand disease. Generally, the more severe the disorder, the more likely the occurrence of ICH. Contact sports and activities can provoke ICH, while safe and noncontact sports present more benefit than danger. An important risk factor is stressful delivery, whether it is prolonged or by vacuum extraction. These should be avoided in patients with congenital bleeding disorders. Familiarity with all risk factors of ICH can help prevent occurrence of this diathesis and reduce related morbidity and mortality.


1996 ◽  
Vol 76 (03) ◽  
pp. 460-468 ◽  
Author(s):  
Francesco I Pareti ◽  
Marco Cattaneo ◽  
Luca Carpinelli ◽  
Maddalena L Zighetti ◽  
Caterina Bressi ◽  
...  

SummaryWe have evaluated platelet function in different subtypes of von Willebrand disease (vWD) by pushing blood through the capillarysized channels of a glass filter. Patients, including those with type IIB vWD, showed lower than normal platelet retention and increased cumulative number of blood drops passing through the filter as a function of time. In contrast, shear-induced platelet aggregation, measured in the cone-and-plate viscometer, was paradoxically increased in type IIB patients. Treatment with l-desamino-8-D-arginine vasopressin (DDAVP) tended to normalize the filter test in patients with type I-platelet normal and type I-platelet low vWD, but infusion of a factor VUI/von Willebrand factor (vWF) concentrate lacking the largest vWF multimers was without effect in type 3 patients. Experiments with specific monoclonal antibodies demonstrated that the A1 and A3 domains of vWF, as well as the glycoproteins Ibα and Ilb-IIIa on platelets, are required for platelet retention in the filter. Thus, the test may reflect vWF function with regard to both platelet adhesion and aggregation under high shear stress, and provide relevant information on mechanisms involved in primary hemostasis.


2015 ◽  
Author(s):  
Lawrence L K Leung ◽  
James L. Zehnder

A bleeding disorder may be suspected when a patient reports spontaneous or excessive bleeding or bruising, often secondary to trauma. Possible causes can vary between abnormal platelet number or function, abnormal vascular integrity, coagulation defects, fibrinolysis, or a combination thereof. This review addresses hemorrhagic disorders associated with quantitative or qualitative platelet abnormalities, such as thrombocytopenia, platelet function disorders, thrombocytosis and thrombocythemia, and vascular purpuras. Hemorrhagic dis­orders associated with abnormalities in coagulation (e.g., von Willebrand disease and hemophilia) are not covered. An algorithm shows evidence-based practice guidelines for the management of immune thrombocytopenic purpura. Tables list questions regarding bleeding and bruising to ask patients, clinical manifestations of hemorrhagic disorders, typical results of tests for hemostatic function in bleeding disorders, causes of thrombocytopenia, other forms of drug-induced thrombocytopenia, classification of platelet function disorders, and selected platelet-modifying agents. This review contains ­1 highly rendered figure, 7 tables, and 82 references. 


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4009-4009
Author(s):  
Diego Mezzano ◽  
Teresa Quiroga ◽  
Manuela Goycoolea ◽  
Blanca Muñoz ◽  
Eduardo Aranda ◽  
...  

Abstract Diagnosis of patients with IMCH is plagued with difficulties: 1. Type 1 VWD (VWD-1) and platelet function disorders (PFD), the best characterized disorders of primary hemostasis, present inherent diagnostic difficulties. 2. Bleeding may be present in healthy individuals and may be absent in patients with diagnosed diseases. 3. An unknown proportion of bleeders do not have an identifiable haemostatic disorder. We studied prospectively 280 consecutive patients (age = 14.5±9.5, range 4–48 years) with family bleeding history who had a high probability of being pathological bleeders, based on an objective bleeding score. Only one physician interviewed the patients and the non-bleeder matched controls, (n=299, age 12.2±6.5, range 4–44 years). Exclusion criteria: age <4 and >50 years; platelet count <100.000/μL; other concurrent diseases, drug intake and C-reactive protein >1mg/dL. VWD was diagnosed when at least two tests (VWF:Ag, VWF:RCo, VWF:CB) had values <percentil 2.5 of the controls, without considering ABO type. PFD were diagnosed by PRP aggregation and 14C-5-HT secretion using pre-established criteria and reference values obtained in the 299 controls. Only 66 (23.6%) of the patients had prolonged bleeding time (BT). Frequency of diseases: 38 (13.6%) patients had VWD-1; 1 (0.35%) had type 2A VWD; 52 (18.6%) had PFD; 8 (2.9%) had concomitant VWD-1 + PFD; 7 patients (2.5%) had mild coagulation factor deficiencies (CFD, 4 with ↓FVIII:C; 2 with ↓ FIX:C; 1 with ↓ FXI:C); and 3 (1.1%) had concomitant VWD-1 + CFD; 171 bleeders (61.1%) had an unknown disorder (UD); in this UD group, 29 (17%) patients had prolonged BT, but all the other hemostatic tests were within the normal range. No distinctive bleeding pattern/severity was found among the above diagnostic categories. One patient with type 2B VWD was excluded because of thrombocytopenia and no patients with type 2N VWD were found. Patients with PFD had a secretion defect, but only 2 of them had typical storage pool disease (↓platelet 5-HT and ADP and ↓ADP/ATP ratio). No phenotypic patterns of Glanzmann or Bernard-Soulier diseases, arachidonate metabolism, or of absent ADP, collagen and TxA2 receptors were observed among the patients with PFD. Interestingly, the 170 patients with UD and the controls had almost the same mean values and distribution of VWF and platelet function variables; so we expect that very few patients with UD would qualify as VWD or PFD in repeated studies. Conclusions: 1. Prevalence of platelet secretion defects is higher than that of type 1 VWD-1 in our population. 2. Types 2 and 3 VWD, as well as paradigmatic platelet disorders (i.e., Glanzmann′s thrombasthenia, Bernard Soulier syndrome) were not detected in this study; they are of very low frequency and they are likely diagnosed at earlier age. 3. Bleeding time lacks sensitivity as a global test of primary haemostasis defects and should be omitted as a diagnostic tool. 4. After a first complete lab workup, 60% of the population with IMCH remains undiagnosed. The overwhelming majority of patients with UD probably constitute a heterogeneous group, independent of VWD or PFD, with a bleeding pattern similar to that of other disorders of primary hemostasis. Hypothetically, structural vascular defects or substances derived from the vascular wall which interfere with the normal platelet-vessel wall interaction could be involved in the pathogenesis of the hemorrhages.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5266-5266 ◽  
Author(s):  
Celine Desconclois ◽  
Vincent Valarche ◽  
Tewfik Boutekedjiret ◽  
Martine Raphael ◽  
Marie Dreyfus ◽  
...  

Abstract Abstract 5266 Diagnosis and characterization of platelet function disorders may be challenging. It requires multiple laboratory data including the assessment of platelet functions. Platelet function analysis is most commonly performed using light transmission aggregometry (LTA). LTA is a time-consuming method requiring centrifugation steps and large blood volumes. It is difficult to perform in children and in cases of thrombocytopenia. In contrast, platelet aggregation in whole blood using impedancemetry (WBI) is a fast method, allows omission of centrifugation steps and performance of platelet function studies under more physiological conditions with small samples size. It is based on the change of resistance proportional to the amount of platelets sticking to two electrodes where an alternating current is applied. Multiplate® (for “multiple electrode aggregometry”, Dynabite Medical) is a new generation of WBI aggregometer using diluted blood and single-use test cells containing twin electrodes that reduce the variation of results. We have already showed the good Multiplate® performance concerning ristocetin-induced platelet aggregation in a population of 30 patients with characterized von Willebrand disease (Valarche et al, 2011). Our aim in this ongoing study was to assess the performance of WBI in patients with inherited platelet function disorders. We tested 8 patients including 2 unrelated patients with Glanzmann Thrombasthenia (GT), 2 unrelated patients with Bernard-Soulier Syndrome (BSS), 1 patient with Gray Platelet Syndrome (GPS) and 3 patients from the same family with a platelet type von Willebrand disease (PTVWD). GT, BSS, and PTVWD diagnosis were confirmed using genotyping. BSS and GPS patients had chronic thrombocytopenia. GT, BSS, GPS and 1/3 PTVWD had platelet function tests with LTA in parallel. WBI was performed on heparinized whole blood diluted at ½ in NaCl at 37°C and triggered using high (0.77 mg/mL, WBI RH) and low (0.5 mg/mL, WBI RL) final ristocetin concentrations, ADP (6.5 Âμ Mol, WBI ADP) and collagen (3.2 Âμg/mL, WBI Coll). Results were expressed in arbitrary unit (AU) corresponding to the area under the aggregation curve observed during 6 min. Normal ranges indicated in brackets were based on the mean +/− 2 SD of 30 healthy volunteers' results. Results highlighted in grey are those out of the normal ranges (Table 1).Table 1:Results of the 8 patients with inherited platelet disorders.PatientsPlatelet count (109/L)WBI RH (AU) [>500]WBI RL (AU) [<150]WBI ADP (AU) [>550]WBI Coll (AU) [>500]GT 116923441443GT 224955417ND7BSS 134371119129BSS 230254733582GPS7916217ND42PTVWD22099493ND338PTVWD231116560ND1092PTVWD2341174168ND852 All patients except those with PTVWD had decreased results with WBI. However, as expected, patients with GT had flat traces using WBI ADP and WBI Coll but normal or only decreased curves (234 – 554 AU) using WBI RH. On the opposite, BSS patients had flat traces using WBI RH but detectable curves using WBI ADP (191 – 335 AU) despite decreased platelet count. The thrombocytopenic GPS patient has a flat trace using WBI Coll and decreased WBI RH (162 AU). Members of the PTVWD family had normal results except a slightly increased result with WBI RH in 1/3 patients. Finally, LTA results performed in 6/8 patients were all in accordance with those of the WBI. In conclusion, in 8 patients with well characterized inherited platelet disorders, WBI was able to detect all abnormalities except PTVWD. In such cases, different ristocetin concentrations use might be critical to increase sensitivity. In our hands, WBI was able to discriminate disorders involving platelet glycoprotein (GP) IIb-IIIa from GP Ib-IX-V: GT patients exhibited flat traces using WBI ADP and WBI Coll, whereas patients with BSS exhibited flat traces with ristocetin. These preliminary results need to be confirmed on a larger population of patients with various characterized platelet function disorders. They suggest that WBI using the Multiplate® analyzer, which is a fast, easy and blood-preserving test, could be a valuable extra step before or in addition to the classic LTA for the diagnosis of severe inherited platelet disorders. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2018 ◽  
Vol 132 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Michael U. Callaghan ◽  
Robert Sidonio ◽  
Steven W. Pipe

Abstract Hemophilia and von Willebrand disease are the most common congenital bleeding disorders. Treatment of these disorders has focused on replacement of the missing coagulation factor to prevent or treat bleeding. New technologies and insights into hemostasis have driven the development of many promising new therapies for hemophilia and von Willebrand disease. Emerging bypass agents including zymogen-like factor IXa and Xa molecules are in development and a bispecific antibody, emicizumab, demonstrated efficacy in a phase 3 trial in people with hemophilia A and inhibitors. Tissue factor pathway inhibitor, the protein C/S system, and antithrombin are targets of novel compounds in development to alter the hemostatic balance and new approaches using modified factor VIII molecules are being tested for prevention and eradication of inhibitor antibodies in hemophilia A. The first recombinant von Willebrand factor (VWF) product has been approved and has unique VWF multimer content and does not contain factor VIII. These new approaches may offer better routes of administration, improved dosing regimens, and better efficacy for prevention and treatment of bleeding in congenital bleeding disorders.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1216-1216
Author(s):  
Lauren E Amos ◽  
Shannon L Carpenter

Abstract Background: Heavy menstrual bleeding (HMB) in adolescents can be severe and life-threatening. Up to 30% of young women who are hospitalized with anemia due to HMB have a bleeding disorder. Guidelines from the American College of Obstetrics and Gynecology (ACOG) and the National Heart, Lung, and Blood Institute (NHLBI) recommend evaluation for bleeding disorders in such patients. ACOG recommendations include testing for von Willebrand disease (VWD) and specify that consultation with a hematologist may help in interpreting results. NHLBI recommends testing for vWD be done in conjunction with a hematologist. As von Willebrand factor is an acute phase reactant, testing when patients are severely anemic and bleeding may not provide accurate results. ACOG guidelines do not include testing for platelet function disorders (PFD), though PFD may be as prevalent as VWD in females with HMB. Early and accurate diagnosis of bleeding disorders is important for health and quality of life, yet limited data exists on the diagnostic evaluation for bleeding disorders in adolescent females hospitalized for HMB. Objectives: To evaluate the diagnostic evaluation of bleeding disorders in adolescent females hospitalized for HMB. Methods: A retrospective, single center chart review of female patients aged 9-21 years hospitalized for HMB and anemia at a tertiary care children's hospital from January 1, 2000 until December 31, 2017 was done. HMB was defined as menses ≥7 days in length, use of 8 or more pads or tampons per day during menses, pictorial bleeding assessment chart (PBAC) score greater than 100, or symptomatic anemia. Patients were identified from our Hemophilia Treatment Center (HTC) registry, review of patients seen at a comprehensive clinic staffed by pediatric hematologists and gynecologists for adolescent females with HMB and bleeding disorders, and by an Electronic Medical Record (EMR) query of admission and discharge diagnoses of HMB and anemia. Data obtained included clinical features, diagnostic evaluation, and laboratory results. Results: 118 patients hospitalized for HMB and anemia were included. Inpatient Hematology consult or outpatient referral occurred in 68 (58%) of the patients; 60/68 (88%) had a bleeding disorder evaluation completed. 34 patients had a hematologic disorder. PFD was the most common (15/34; 44%) followed by VWD (9/34; 26%). 42% (50/118) of the patients did not have a Hematology consult or outpatient referral (Table 1). While hospitalized for HMB and anemia, 29 of the 50 patients had testing for vWD performed and only 4/29 (14%) had testing repeated as an outpatient once hemoglobin normalized. No patients tested for VWD while inpatient had results consistent with the diagnosis. Platelet function testing was performed in 10/50 patients using the platelet function analyzer (PFA-100) in 8 patients and platelet aggregometry in 2 patients. Conclusions: Despite national guidelines and the presence of known risk factors such as HMB since menarche and HMB causing severe anemia, the hematology service was not involved in the diagnostic process for a significant number of adolescent females. In these patients, testing often occurred while patients were hospitalized and was not repeated. Testing for platelet function disorders occurred infrequently and mainly consisted of the PFA-100 which lacks sensitivity and specificity. When patients were evaluated by Hematology and tested for bleeding disorders, a large proportion had a bleeding disorder, of which PFD were most common. This study demonstrates the need for standardization of the evaluation of adolescent females hospitalized for HMB. Guidelines should be updated to include testing for PFD. Hematologists should be involved when females are hospitalized for HMB and anemia. Disclosures Carpenter: Genentech Incorporated: Membership on an entity's Board of Directors or advisory committees; Nationwide Children's Hospital: Speakers Bureau; Bayer: Honoraria; Kedrion Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk Pharmaceuticals, Inc: Consultancy; HEMA Biologics: Consultancy; American Academy of Pediatrics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novo Nordisk: Consultancy; National Hemophilia Foundation (Impact Education): Speakers Bureau; Kane County State's Attorney: Consultancy; CSL Behring: Speakers Bureau; 4th Judicial District Attorney's Office- Colorado: Consultancy; Kedrion Biopharmaceuticals: Consultancy.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4937-4937
Author(s):  
Nazli Hossain ◽  
Tahir S. Shamsi ◽  
Arshi Naz ◽  
Sidra Abbas ◽  
Nazeer Khan

Abstract Introduction: Inherited bleeding disorders are an important cause of menorrhagia. Aim: To determine the prevalence of inherited bleeding disorders in women with menorrhagia in the absence of systemic and pelvic pathologies. Methods: The study period was from March 2013 to September 2018. It was carried out at the Department of Obstetrics & Gynecology, Unit II, Dow Medical College and Ruth Pfau KM Civil Hospital in Karachi. The laboratory investigations were carried out partly at Dow Diagnostic Research Laboratory and mainly at the National Institute of Blood Disease & Bone Marrow Transplant. Included in the study were young girls and women who presented with menorrhagia at menarche or in the later years of reproduction, with normal bimanual pelvic examination and pelvic ultrasound results. Results: Approximately 200 women with a mean menstrual cycle duration of 9.3+ 3.5 days were included. The mean age of the included patients was 32 years. Married women's partners were cousins in 50% of the women, while unmarried girls' parents were cousins in all cases. Platelet aggregation defect was presented in 33 (16.6%) women, von Willebrand disease in 26 (13.1%) women, factor IX deficiency in 20 (10%) women, combined defects in 29 (14.6%) women, and factor VII and VIII deficiencies in 4 and 11 (2%, 5.5%) women, respectively. Isolated defect with ADP, epinephrine, and collagen were decreased in 35 (17.6%), 41 (20%), and 33 (16%) women, respectively. Conclusion: Inherited bleeding disorders were a common cause of menorrhagia in our population. Consanguinity was frequently seen in these subjects. Except for some forms of VWD, all other disorders have an autosomal recessive inheritance pattern. After excluding gynecological and medical causes, a work up for inherited bleeding disorders should be advised. Keywords: menorrhagia, platelet function disorder, inherited bleeding disorders, Pakistan. Disclosures No relevant conflicts of interest to declare.


2005 ◽  
Vol 11 (3) ◽  
pp. 325-330 ◽  
Author(s):  
Meenal Gupta ◽  
Maitreyee Bhattacharyya ◽  
V. P. Choudhry ◽  
Renu Saxena

The incidence of hereditary hemorrhagic disorders may vary according to the country and ethnic origin. Von Willebrand disease has emerged as the most common hereditary hemorrhagic disease in the industrialized world. In this series of 966 patients diagnosed to have inherited bleeding disorders, hemophilia A was the most common and was seen in 410 (42.4%) of the patients followed by platelet function defects seen in 380 (39.4%) of the patients. It is thus concluded that, similar to the white population, hemophilia A remains the most common bleeding disorder in the Indian population, although this is closely followed by platelet function defects in India, which are quite rare in whites. Von Willebrand disease is relatively rare in the Indian population.


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