BERNARD SOULIER SYNDROME IN PREGNANCY

2021 ◽  
pp. 17-19
Author(s):  
Malini Sukayogula ◽  
Manisha Pradhan ◽  
Tarakeswari Surapaneni
Keyword(s):  
Autosomal Recessive ◽  
Postpartum Haemorrhage ◽  
Von Willebrand Disease ◽  
Factor Vii ◽  
Thrombocytopenic Purpura ◽  
Giant Platelet ◽  
Platelet Disorder ◽  
Von Willebrand ◽  
Bernard Soulier Syndrome ◽  
Autosomal Recessive Pattern

Bernard-Soulier syndrome is an inherited platelet disorder, transmitted in an autosomal recessive pattern. Thrombocytopenia and large defective platelets are characteristics, often presents early with bleeding symptoms, such as epistaxis, ecchymosis, menometrorrhagia, and gingival or gastrointestinal bleeding. Diagnosis can be conrmed by platelet aggregation studies and ow cytometry. Differential diagnosis includes other inherited giant platelet disorders, as well as von Willebrand disease and immune thrombocytopenic purpura. During pregnancy, it can present as recurrent rst trimester miscarriages, antepartum, intrapartum and postpartum haemorrhage. Treatment remains generally supportive with platelet transfusions and recombinant factor VII has also been described in literature.

Bernard-Soulier Syndrome: An Inherited Platelet Disorder

2007 ◽  
Vol 131 (12) ◽  
pp. 1834-1836 ◽  
Author(s):  
Angie Pham ◽  
Jun Wang
Keyword(s):  
Von Willebrand Disease ◽  
Factor Vii ◽  
Recombinant Activated Factor Vii ◽  
Giant Platelet ◽  
Activated Factor Vii ◽  
Platelet Disorder ◽  
Immune Thrombocytopenia Purpura ◽  
Von Willebrand ◽  
Bernard Soulier Syndrome ◽  
Autosomal Recessive Manner

Abstract Bernard-Soulier syndrome is an inherited platelet disorder, which is transmitted in an autosomal recessive manner. This syndrome is characterized by variable thrombocytopenia and large defective platelets. Bernard-Soulier syndrome often presents early with bleeding symptoms, such as epistaxis, ecchymosis, menometrorrhagia, and gingival or gastrointestinal bleeding. Diagnosis can be confirmed by platelet aggregation studies and flow cytometry. The differential diagnosis includes the other inherited giant platelet disorders, as well as von Willebrand disease and immune thrombocytopenia purpura. Treatment is generally supportive with platelet transfusions when absolutely necessary and avoidance of antiplatelet medications. Recombinant activated factor VII and desmopressin have been used in attempts to shorten bleeding times; however, no definitive studies regarding their effectiveness have been reported.

Haematopathology

2012 ◽  
Author(s):  
James Carton
Keyword(s):  
Iron Deficiency Anaemia ◽  
Dehydrogenase Deficiency ◽  
Hereditary Spherocytosis ◽  
Von Willebrand Disease ◽  
Thrombocytopenic Purpura ◽  
Deficiency Anaemia ◽  
Anaemia Of Chronic Disease ◽  
Sickle Cell Disorders ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Von Willebrand

Iron deficiency anaemia 256Anaemia of chronic disease 257Megaloblastic anaemias 258Hereditary spherocytosis 259Glucose-6-phosphate dehydrogenase deficiency 260Thalassaemias 261Sickle cell disorders 262Idiopathic thrombocytopenic purpura 264Thrombotic thrombocytopenic purpura 265von Willebrand disease 266Haemophilia 267Thrombophilia 268Acute B-lymphoblastic leukaemia 269...

scholarly journals Screening for von Willebrand Disease With a New Analyzer Using High Shear Stress: A Study of 60 Cases

Blood ◽  
1998 ◽  
Vol 91 (4) ◽  
pp. 1325-1331 ◽  
Author(s):  
Edith Fressinaud ◽  
Agnès Veyradier ◽  
Florence Truchaud ◽  
Isabelle Martin ◽  
Catherine Boyer-Neumann ◽  
...  
Keyword(s):  
Shear Stress ◽  
High Sensitivity ◽  
Adenosine Diphosphate ◽  
Normal Subjects ◽  
Von Willebrand Disease ◽  
High Shear ◽  
High Shear Stress ◽  
Platelet Disorder ◽  
Von Willebrand

AbstractWe have evaluated the performance of a new analyzer using high shear stress, the PFA-100 (Platelet Function Analyzer, Dade International, Massy, France), for screening of patients with von Willebrand disease (vWD). Whole citrated blood is aspirated through a capillary to the central aperture of a membrane coated with collagen and with a platelet agonist (either epinephrine or adenosine diphosphate [ADP]). The time required to obtain occlusion of the aperture by a platelet plug is defined as the closure time (CT). We studied 60 patients with different types of vWD and 96 normal subjects. Fourteen subjects with hemophilia and 15 patients with a platelet disorder were also analyzed. When omitting results from two patients with type 2N, the 58 other patients with type 1, type 2A, type 2B, type 3, or acquired vWD all exhibited an abnormal occlusion with collagen-ADP (sensitivity, 100%) and 56 of 58 had an abnormal CT with collagen-epinephrine (sensitivity, 96.5%). Only two patients with mild type 1 were not detected with collagen-epinephrine. In comparison, the bleeding time (BT) was normal in 20 patients: 17 with type 1, two with type 2A, and one with acquired vWD (sensitivity, 65.5%). The specificity of the PFA-100 was over 95% with both types of cartridges. Thus, the analyzer is well adapted to routine testing, as it has the advantages of simplicity and ease of execution, and demonstrates a high sensitivity, clearly superior to that of BT, for the screening of patients with vWD.

Use of Recombinant Factor VIIa (rVIIa) for Treatment of Bleeding in Type II B Von Willebrand Disease: A Case Report

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4514-4514
Author(s):  
Arash Rezazadeh ◽  
Patricia P Ashby ◽  
Vivek R. Sharma
Keyword(s):  
Case Report ◽  
Hormonal Therapy ◽  
Von Willebrand Disease ◽  
Coagulation Cascade ◽  
Factor Vii ◽  
Severe Reaction ◽  
Platelet Surface ◽  
First Case ◽  
Gi Bleed ◽  
Von Willebrand

Abstract Background: Von Willebrand disease (vWD) is an inherited bleeding disorder caused by a deficiency or dysfunction of von Willebrand’s factor (VWF). Type 2 vWD is a qualitative deficiency of VWF with the IIB variant being caused by a “gain of function” mutation that results in increased affinity of the vWF for platelet GPIb. Treatment of choice for bleeding episodes is factor VIII-VWF concentrate or DDAVP in selected cases. We are reporting a case of type IIB vWD where rVIIa was used successfully for hemostasis. Case report: A 28 year old white female with type IIB vWD had being doing well with Humate-P® which she used most frequently for menorrhagia. She had also been treated successfully with Humate-P® for peri-operative hemostasis during back surgery but approximately 3 years after this developed anaphylactic reaction while getting humate-P for an episode of severe menorrhagia. A test dose of a different lot of Humate-P® in the hospital also resulted in a severe reaction. Administration of Koâte®-DVI and Alphanate® was subsequently attempted but caused similar anaphylactic reactions after the first few doses. She had normal IgA levels. Amicar and hormonal therapy was used to control the menorrhagia to where she was able to maintain a relatively stable Hgb level and not require frequent PRBC transfusion. Unfortunately, a few months later the patient developed GI bleeding from what was initially an occult source and ended up needing upwards of 40 units of PRBC transfusion over a period of two months. She was offered options of trying cryoprecipitate as well as DDAVP but refused after weighing the risks and benefits. At this time, rVIIa was given and the bleeding appeared to slow down resulting in lesser frequency of transfusion but it did not entirely stop. After several unsuccessful attempts to locate the source, a tagged RBC study finally found the bleed originating near the cecal area which eventually turned out to be a malignant ileocecal carcinoid that had been missed on initial colonoscopy as well as on capsule camera endoscopy. There was no clincally overt carcinoid syndrome. Patient underwent a right hemicolectomy and received rVIIa perioperatively according to the protocol approved for patients with hemophilia with factor inhibitor. She received NovoSeven® 90 mcg/kg before the surgery and then q2h for the first 24 hours. She had rVIIa q3h on post-op day one. The dose frequency was dropped to q4h on day 2 followed by q6h on post-op days 3 to 7. This provided excellent perioperative hemostasis. She has done well with no further GI bleed or recurrence of the tumor after more than a year and her menorrhagia is fairly well controlled with hormonal therapy and amicar. Discussion: Factor VII, a vitamin K-dependent glycoprotein, promotes hemostasis by activating the extrinsic pathway of the coagulation cascade. Although it does not affect the vWF level it probably bypasses the deficiency via thrombin generation on platelet surface. In literature search we found two case reports regarding utilizing rFVII in vWD, both with uncontrolled bleeding despite adequate factor replacement. First case with acquired vWD and GI bleed and the second case was inherited vWD with GI angiodysplasia. The precise mechanism of action in this setting however is not fully understood. Conclusion: To our knowledge this is the first report of utilizing rVIIa in a patient intolerant to vWF without inhibitors to vWF. rVIIa should be considered a viable option for hemostasis in patients unable to tolerate vWF due to severe allergy.

scholarly journals Platelet dysfunction in platelet-type von Willebrand disease due to the constitutive triggering of the Lyn-PECAM1 inhibitory pathway

Haematologica ◽  
2021 ◽  
Author(s):  
Loredana Bury ◽  
Emanuela Falcinelli ◽  
Anna Maria Mezzasoma ◽  
Giuseppe Guglielmini ◽  
Stefania Momi ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Von Willebrand Disease ◽  
Bleeding Tendency ◽  
Platelet Dysfunction ◽  
Platelet Disorder ◽  
Granule Secretion ◽  
Inhibitory Signaling ◽  
Von Willebrand ◽  
First Time ◽  
Willebrand Factor

Platelet-type von Willebrand disease (PT-VWD) is an inherited platelet disorder characterized by macrothrombocytopenia and mucocutaneous bleeding, of variable severity, due to gain-of-function variants of GP1BA conferring to glycoprotein Ibα (GPIbα) enhanced affinity for von Willebrand factor (VWF). The bleeding tendency is conventionally attributed to thrombocytopenia and large VWF-multimers depletion. Some clues, however, suggest that platelet dysfunction may contribute to the bleeding phenotype but no information on its characteristics and causes are available. Aim of the present study was to characterize platelet dysfunction in PT-VWD and shed light on its mechanism. Platelets from a PT-VWD patient carrying the p.M239V variant and from PT-VWD mice carrying the p.G233V variant showed a remarkable platelet function defect, with impaired aggregation, defective granule secretion and reduced adhesion under static and flow conditions. VWF-binding to GPIbα is known to trigger intracellular signaling involving Src-family kinases (SFKs). We found that constitutive phosphorylation of the platelet SFK Lyn induces a negative-feedback loop downregulating platelet activation through phosphorylation of PECAM1 on Tyr686 and that this is triggered by the constitutive binding of VWF to GPIbα binding. These data show for the first time that the abnormal triggering of inhibitory signals mediated by Lyn and PECAM1 may lead to platelet dysfunction.In conclusion, our study unravels the mechanism of platelet dysfunction in PT-VWD caused by deranged inhibitory signaling triggered by the constitutive binding of VWF to GPIbα which may significantly contribute to the bleeding phenotype of these patients.

Haematopathology

2017 ◽  
Author(s):  
James Carton
Keyword(s):  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Primary Myelofibrosis ◽  
Von Willebrand Disease ◽  
Polycythaemia Vera ◽  
Primary Amyloidosis ◽  
Thrombocytopenic Purpura ◽  
Hodgkin's Lymphomas ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Von Willebrand

This chapter discusses haematopathology, including iron deficiency anaemia, anaemia of chronic disease, megaloblastic anaemias, hereditary spherocytosis, glucose-6-phosphate dehydrogenase deficiency, thalassaemias, sickle-cell disorders, idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), von Willebrand disease, haemophilia, thrombophilia, acute B-lymphoblastic leukaemia, acute myeloid leukaemias, chronic lymphocytic leukaemia (CLL), chronic myelogenous leukaemia, polycythaemia vera (PV), essential thrombocythaemia (ET), primary myelofibrosis (PMF), myelodysplastic syndromes (MDS), follicular lymphoma, diffuse large B-cell lymphoma, Burkitt’s lymphoma (BL), extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), mantle cell lymphoma, classical Hodgkin’s lymphoma (cHL), lymphoplasmacytic lymphoma (LPL), plasma cell myeloma, primary amyloidosis, and mature T-cell non-Hodgkin’s lymphomas.

Whole Blood Impedance Aggregometry: A New Tool for Severe Inherited Platelet Disorder Diagnosis?

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5266-5266 ◽  
Author(s):  
Celine Desconclois ◽  
Vincent Valarche ◽  
Tewfik Boutekedjiret ◽  
Martine Raphael ◽  
Marie Dreyfus ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Whole Blood ◽  
Von Willebrand Disease ◽  
Fast Method ◽  
Normal Ranges ◽  
Platelet Function Disorders ◽  
Platelet Disorder ◽  
Platelet Disorders ◽  
Von Willebrand

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.

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