Acquired Glanzmann Thrombasthenia in a Pediatric Patient with Alagille Syndrome

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S101-S101
Author(s):  
C A Cox ◽  
H Hastings
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Alagille Syndrome ◽  
Bleeding Disorder ◽  
Solid Organ ◽  
Glanzmann Thrombasthenia ◽  
Normal Platelet ◽  
Normal Limits ◽  
Mucocutaneous Bleeding ◽  
Platelet Antibody

Abstract Introduction/Objective Acquired Glanzmann Thrombasthenia is a rare bleeding disorder that is characterized by inhibition of glycoprotein IIb/IIIa signaling, usually by an autoantibody, leading to an interference in platelet aggregation. Clinically, this disorder presents with spontaneous mucocutaneous bleeding in the setting of a normal platelet count. Acquired Glanzmann Thrombasthenia has been associated with primary immune thrombocytopenic purpura (ITP), several types of hematologic and solid malignancies, solid organ transplants, and other autoimmune disorders. Methods/Case Report A 4-year-old female patient with a history of Alagille Syndrome requiring liver transplant at age 3 was admitted to the hospital after presenting to the emergency department with complaints of bruising, nosebleeds, and a petechial rash. The patient was found to have a platelet count of 11 K/mm3 and was diagnosed with ITP. The patient received a single dose of IVIG at 1g/kg with subsequent resolution of bleeding and a recovering platelet count of 27 K/mm3 12 hours after administration. However, two months later, the patient presented again with worsening bruising, multiple nosebleeds per day, and worsening petechiae. Lab studies revealed the patient’s platelet count was within normal limits. A platelet antibody screen was positive with a subsequent Platelet Antibody Bead Array revealing anti-Gp IIb/IIIa HPA-1 and HPA-3 positivity. Results (if a Case Study enter NA) N/A Conclusion Acquired Glanzmann Thrombasthenia is a rare bleeding disorder that is the result of interference with platelet aggregation. Antibodies that may be associated with any of several underlying conditions lead to impaired platelet function and subsequent mucocutaneous bleeding. The present case represents an occurrence of Acquired Glanzmann Thrombasthenia in a patient with multiple risk factors for development of the disorder.

Low Platelet Counts: Diagnosis Using Flow Cytometry and Anti Platelet Antibody.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3966-3966
Author(s):  
Joao Carlos C. Guerra ◽  
Ruth H. Kanayama ◽  
Sonia S. Nozawa ◽  
Marcia R. Ioshida ◽  
Irina Y. Takihi ◽  
...  
Keyword(s):  
Platelet Count ◽  
Direct Method ◽  
Biochemical Tests ◽  
Platelet Counts ◽  
Normal Platelet ◽  
Laboratory Error ◽  
Unusual Phenomenon ◽  
Reference Service ◽  
Children And Young Adults ◽  
Platelet Antibody

Abstract In our service of hematology 9,1 % of all consults are related to low platelet number finding in the CBC. Pseudothormbocytopenia is a rather unusual phenomenon, induced by agglutination of platelets by auto-antibodies acting on EDTA collected blood. Objective: Classify, diagnose and analyze low platelet counts as obtained by automatic blood counters. Methods: From January 1997 to May 2005; 16761 patients were attended in our service. Among them, 1174 cases (7,0%), 429 males and 745 females (1 to 75 years), were there because of low platelet counts alone. Platelet counts were done by Coulter T-890, with blood collected in EDTA K3 and sodium citrate. Counts were repeated after letting blood at 4o C for 24 hours; also Fonio technique and Neubauer camera counts were done. Normal value was defined as platelet count between 150,000 to 450,000. Bone marrow was obtained when necessary and stained by conventional techniques. Serological and biochemical tests were done in a Cobas Core (Roche) machine. Immuno-phenotyping was done in 115 cases, to identify anti-platelet-antibody (CD41 PE Immunotech and anti human IgG FTIC conjugate Sigma)-direct method, by flow citometry (Coulter Epics XL-MCL). Results: Among the 1158 cases, platelets counts between 120 000 to 150 000, were found in 15.8 %; laboratory error in 6,3 % and spurious low platelet counts in 1.3 %. In addition, the follow up for four years of those patients with “lower normal” platelet count (120 000 to 150 000) did not show any morbid process. Immunologycal idiopatic purpura (ITP) was diagnosed in 49,1 % of the cases, being as expected, more frequent in females, children and young adults. Hepatitis C as cause of low platelet counts was responsible for 6,9 % and HIV infection for 1.3 % of the cases Anti-platelet antibodies were present in 76.9 % of ITP cases and was not found in 88.3 % of normal platelet values. Conclusions: In an hematological reference service should be considered a lower range for normal platelet values (120 000 to 450 000). Additionally, low platelet counts as diagnosed by automated machines should be confirmed by slide exam and anti platelet antibody is useful for asserting ITP diagnosis and to rule out spurious thrombocytopenia or normal values.

Evaluation of Children with Suspected Bleeding Disorder Applying the Impact-R [Cone and Plate(let) Analyzer].

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3962-3962 ◽  
Author(s):  
Shoshana Revel-Vilk ◽  
Esther Hyam ◽  
Tali Zelikowitz ◽  
Ela Shai ◽  
David Varon
Keyword(s):  
Platelet Aggregation ◽  
Factor Viii ◽  
Platelet Function ◽  
Predictive Value ◽  
Bleeding Disorder ◽  
Measurement Sensitivity ◽  
Normal Platelet ◽  
Function Defect ◽  
Bleeding History ◽  
The Impact

Abstract Background: von Willebrand’s disease (VWD) is the most common bleeding disorder, affecting between 1–10% of the general population. There is a need for a simple test to screen patients with bleeding symptoms before more labor-intensive diagnostic steps are taken. The Impact-R [Cone and Plate(let) Analyzer (CPA)] (DiaMed Switzerland), was designed in an attempt to test platelet function under close to physiological conditions. Citrated whole blood is applied on polystyrene surface, under controlled shear conditions using a cone and plate device, followed by a quantitative analysis of platelet deposition to immobilized plasma von Willebrand’s factor (VWF) and fibrinogen. Results of the test are presented for adhesion as % surface coverage (SC) and for aggregation as average size (μm2, AS). In this study we report the use of CPA test in evaluation of children with suspected bleeding disorder. Methods: Fifty-four consecutive children with bleeding symptoms and normal platelet count and coagulation tests were evaluated between August 1st, 2006 and July 31, 2007. In addition to the CPA test, all children were tested for VWF: antigen plasma level, VWF: ristocetin activity, factor VIII: C plasma level, platelet aggregation test using turbidometric aggregometer (Helena, USA) and blood type. The study was approved by the local Helsinki committee. Statistical analysis was done by SPSS. Results: Of 54 children, 10 (18.9%) were diagnosed with VWD and 6 (11.1%) children were diagnosed with platelet function defect according to bleeding history, family history, aggregation and factor VIII/VWF tests. To test the validity of the CPA as a screening test for diagnosis of VWD and platelet function defects a ROC curve was formulated for both SC and AS measurements. The best cutting point for a positive test was equal or less then 6.5% for SC measurement (sensitivity 60%, specificity 65%), and equal or lest then 26.5μm2 for AS measurement (sensitivity 67%, specificity 81.6%). The predictive value of a normal CPA test (negative predictive value), i.e. SC > 6.5% and AS > 26.5μm2, was 92%. Of the 26 normal CPA tests, one child was diagnosed with mild type I VWD and one child was diagnosed with mild platelet defect in response to epinephrine (40%). The predictive value of an abnormal CPA test (positive predictive value) was 50%. Of the 28 abnormal CPA test, 9 children were diagnosed with VWD, 4 children with platelet defect in response to epinephrine (<30%) and one child with platelet defect in response to collagen (10%). Significant bleeding symptoms (bleeding score 3 or more) were reported in 4 of 14 children with abnormal CPA test but with normal VWF, normal factor VIII and normal platelet aggregation. Conclusions: The CPA test was found to be a useful tool for excluding VWD and platelet function defect in children suspected for bleeding disorder. Yet, in case of an abnormal CPA test, further testing are needed. Interestingly, abnormal CPA test was the only finding in some children with a significant bleeding history, suggesting other underlying adhesion defects yet to be described.

First Report of Transheterozygosity in a Patient with An Inherited Platelet Bleeding Disorder Due to Mutations in the Thromboxane A2 Receptor (TBXA2R) and cyclooxygenase1 (PTGS1),

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3260-3260
Author(s):  
Kathleen Freson ◽  
Chantal Thys ◽  
Christel Van Geet
Keyword(s):  
Platelet Aggregation ◽  
Autosomal Recessive ◽  
Conflicts Of Interest ◽  
Autosomal Recessive Disorder ◽  
Bleeding Disorder ◽  
Bleeding Complications ◽  
Normal Platelet ◽  
First Case ◽  
Functional Defect ◽  
Sequencing Platforms

Abstract Abstract 3260 Platelet aggregation by thromboxane (TBXA2) stimulation of its G protein-coupled receptor TXA2R is initiated after conversion of arachidonic acid (AA) into prostaglandin H2 (PGH2) by cyclooxygenase1 (PTGS1) and subsequently by conversion of PGH2 into TXA2 by thromboxane synthase (TBXAS1). Hirata et al (JCI, 1994) reported the first TBXA2R mutation that resulted in reduced platelet responses to U46619 and low AA concentrations in subjects with a heterozygous R60L mutation. This functional defect in combination with mild clinical bleeding problems was only described for the one patient that was homozygous for this mutation. A second TBXA2 patient with an obvious bleeding diathesis carried a heterozygous D304N mutation but it was reported that this variant by itself could not explain the bleeding phenotype as other family members heterozygous for D304N presented with abnormal aggregation responses but no bleeding problems (Mumford, Blood, 2010). Functional SNPs in PTGS1 were described in pharmacogenetic studies including the L237M variant with 50% reduced COX1 metabolic activity but its effect on platelet function was not studied (Lee CR, Pharmacogenet Genomics, 2007). We here describe a 6-year old patient with ecchymosis, easy bruising and important post-traumatic bleeding complications after adenotonsillectomy and circumcision. The boy presents with normal coagulation parameters, normal platelet count and MPV, structurally normal platelets, normal ATP secretion by collagen, and the PFA100 closure time was normal for Col/Epi and mildly prolonged for Col/ADP. Platelet aggregation studies further showed an absent response to 1 mM AA as determined on different occasions, a reduced but not absent response to U46619 and a normal activation with ADP, ristocetin and Horm collagen. His parents and sister presented with increased sensitivity for ecchymoses but none had severe clinical bleeding problems and their platelets showed normal aggregation responses except for the father and sister with a reduced though not absent response to AA. Thromboxane B2 formation was determined and found to be normal in basal (plasma) and maximal stimulated (serum) conditions. In contrast, TXB2 levels were decreased after activation with U46619 for the patient but also for the father and sister compared to the control or mother. Activation with AA also resulted in reduced TXB2 levels for the patient and mildly reduced levels for all other family member compared to controls. This strongly suggests the presence of an autosomal recessive disorder. The TBXAS1, PTGS1 and TBXA2R genes were sequenced for the patient and we identified two heterozygous mutations in separate genes being R60H in TXBA2R and the functional L237M variant in PTGS1. Interestingly, his mother carried the L237M variant while R60H was present in father and sister with similar functional platelet defects as earlier described for the other heterogenous TBXA2R mutations but no clinical bleeding symptoms. To our knowledge, this is the first case of transheterozygosity for mutations explaining an autosomal recessive bleeding disorder. We hypothesize that this pattern of inheritance might be more common than expected and therefore this possibility should be taken into account when analyzing patients in the future using exome or genome wide sequencing platforms. Disclosures: No relevant conflicts of interest to declare.

Study of a Caucasian Family with von Willebrand’s Disease in Association with Vascular Telangiectasia and Hemoglobinopathy

1979 ◽  
Author(s):  
W. Hanna ◽  
C. McCarroll ◽  
J. Chen ◽  
T. McDonald ◽  
D. Lin ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Factor Viii ◽  
Bleeding Time ◽  
Family Members ◽  
Inherited Disorders ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Normal Platelet ◽  
Coagulant Activity

This family carries multihematological inherited disorders; namely, von Wille-brand’s, vascular telangiectasia and hemoglobinopathy. Family members were studied by quantifying the following: Factor VIII pro-coagulant activity, Factor VIII related antigen, Factor VIII inhibitors, platelet adhesion, platelet aggregation (with ristocetin, collagen and ADP), bleeding time, platelet count, partial thromboplastin time, prothrombin time, hemoglobin electrophoresis, hemoglobin finger-printing, sickling preparation and the presence of telangiectasia.The affected members of this family with von Willebrand’s express their disease in a variable tendency to bleeding from almost clinically asymptomatic cases to cases with severe bleeding tendency.One member of this family had to have a hysterectomy at the age of 20 to control the abnormal uterine bleeding after conservative treatment failed. All affected members with von Willebrand’s disease had a normal platelet count, prolonged bleeding time, decreased Factor VIII pro-coagulant activity and related antigen, negative aggregation using the ristocetin co-factor for von Willebrand’s, defective platelet adhesiveness to glass beads, and normal platelet aggregation to collagen and ADP. Some members have vascular telangiectasia in the mucous membranes. An incidental finding was the presence of an abnormal hemoglobin S in some family members.Supported in part by the Cumberland Chapter of the National Hemophilia Foundation.

scholarly journals Plasma Fibrinogen Level, Platelet Aggregation and Platelet Count in Stable Angina

1970 ◽  
Vol 8 (2) ◽  
pp. 57-59
Author(s):  
Momotaj Begum ◽  
Ma Hai ◽  
ASM Lokman Hossain Chowdhury ◽  
Noorjahan Begum
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Stable Angina ◽  
Healthy Subjects ◽  
Fibrinogen Level ◽  
Plasma Fibrinogen ◽  
Background Information ◽  
Plasma Fibrinogen Level ◽  
Normal Platelet ◽  
A Prospective Study

This was a prospective study. The study was done from July 1997 to June 98. All the cases were selected from the outdoor patients of National Institute of Cardiovascular Diseases (NICVD), Controls were selected from healthy volunteers. The plasma fibrinogen level, platelet aggregation and platelet count were studied on a total number of 35 subjects with age ranged from 40-60 years of both sexes. Of these 20 were normal healthy subjects and 15 were patients with stable angina. Plasma fibrinogen level were normal as like as healthy subjects. Platelet aggreagations were increased in some cases but others show normal findings. The platelet count were slightly decreased but it was within normal range. Form this study it may be observed that normal plasma fibrinogen level and increased platelet aggregation with normal platelet count may occur in patients with stable angina. The increased platelet aggregation indicate hypercoagulable states which may aggravate the condition of patients with stable angina and this is the risk factor for the further development of severe ischemia of the heart. So, the routine investigation of plasma fibrinogen level, platelet aggregation and platelet count may be helpful to utilize them as background information both for therapeutic and preventive measures in patients with stable angina.     DOI = 10.3329/jom.v8i2.1408 J MEDICINE 2007; 8 : 57-59

scholarly journals Clinical and Experimental Studies on the Bleeding Tendency During Defibrinogenation Therapy

1977 ◽  
Author(s):  
S. Ishimaru ◽  
K. Furukawa ◽  
M. Takahashi ◽  
M. Fujimaki ◽  
K. Fukutake
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Surgical Procedure ◽  
Postoperative Bleeding ◽  
Experimental Studies ◽  
Bleeding Complications ◽  
Fibrinogen Concentration ◽  
Bleeding Tendency ◽  
Normal Platelet ◽  
Normal Limits

Defibrinogenation with thrombin-like enzyme is expected to be a new type of anticoagulant therapy without serious bleeding complications. However, it appears to be dangerous to perform surgical procedure in defibrinogenated state. In order to investigate the causes of the bleeding tendency which occurs during defibrinogenation therapy, the following clinical and experimental studies were undertaken. Ten mongrel dogs were used, the superior caval vein was replaced by expanded polytetrafluoroethylene graft. 50 to 100 μl/kg of batroxobin was administered 2 days prior to the operation. 5 out of 10 dogs died due to bleeding postoperativelly, and the causes of the bleeding seemed to be the decreased fibrinogen concentration and the reduced platelet function. Fifteen patients suffering from peripheral vascular thrombosis were treated with 30 to 60 μl/kg of batroxobin. In 9 patients, urokinase was administered combined with batroxobin. No bleeding complications were observed in these patients. In another 6 patients, surgical procedure was performed after batroxobin administration. Postoperative bleeding was observed in one out of these 6 patients. This patient was operated on after the initial administration of batroxobin. FDP level was 512 μg/ml and ADP induced platelet aggregation was within normal limits, but fibrinogen concentration was unmeasurable at the time of operation. The cause of the bleeding seemed to be the decreased fibrinogen concentration. From these clinical experiences, it is suggested that platelet adhesion to glass and ADP induced platelet aggregation are not influenced by the decreased fibrinogen concentration nor the increased level of FDP during the defibrinogenation therapy with batroxobin. These results indicate that an adequate level of fibrinogen is needed for certain hemostasis besides normal platelet function.

Evaluation of the Gene Encoding Calcium Diacylglycerol Guanine Nucleotide Exchange Factor I (CalDAG-GEFI) in Human Patients with Congenital Qualitative Platelet Disorders.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5078-5078
Author(s):  
John Puetz ◽  
Mary Boudreaux
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Factor I ◽  
Normal Platelet ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Platelet Function Disorders ◽  
Mucocutaneous Bleeding

Abstract Abstract 5078 Normal platelet function is dependent on an orchestrated series of interactions resulting in primary hemostasis. Dysfunction in any step of platelet activation and aggregation results in abnormal platelet function and abnormal mucocutaneous bleeding. Defects in agonist/receptor interactions, membrane phospholipid and cytoskeleton structure, signal transduction, storage pool content and release have all been described. While some congenital qualitative platelet function disorders such as Bernard-Soulier syndrome or Glanzmann thrombasthenia are well characterized at the molecular and genetic level, the majority of congenital platelet function disorders are not. Recently, insights into the molecular and genetic causes of platelet signal transduction and secretion pathway disorders have been found in animals. Dogs and cattle with recurrent abnormal mucocutaneous bleeding symptoms and abnormal in vitro platelet aggregation have been found to be caused by a mutation in the calcium-diacylglycerol guanine nucleotide exchange factor I (CalDAG-GEFI) gene. Genetic ablation of CalDAG-GEFI in mice has resulted in abnormal platelet function and bleeding. Polymorphisms in the human CalDAG-GEFI gene have been linked to Kindlin-3/ FERMT3 mutations resulting in a leukocyte adhesions defect associated with platelet dysfunction (LAD-III or LAD-1/variant syndrome). To date, mutations in the CalDAG-GEFI gene in humans associated with abnormal platelet function and bleeding have not been described. To determine if mutations in the human CalDAG-GEFI gene are associated with abnormal mucocutaneous bleeding and platelet aggregation dysfunction, we have begun sequencing the CalDAG-GEFI gene in human patients with a congenital qualitative platelet function disorder of unknown etiology. As control groups, we will also evaluate the CalDAG-GEFI gene sequence of unaffected family members and unrelated blood donors known to have normal platelet aggregation. Preliminary results of our analysis will be presented. Disclosures No relevant conflicts of interest to declare.

Effect of Purified Vipera Palestinae Hemorrhagin on Blood Coagulation and Platelet Function

1969 ◽  
Vol 22 (03) ◽  
pp. 482-495 ◽  
Author(s):  
L Grotto ◽  
Z Jerushalmy ◽  
A de Vries
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Connective Tissue ◽  
Blood Coagulation ◽  
Guinea Pigs ◽  
Clotting Time ◽  
Clot Retraction ◽  
Normal Platelet Count ◽  
Normal Platelet ◽  
Adp Release

SummaryPurified Vipera palestinae hemorrhagin (VPH) impairs thrombin formation, fibrinogen clottability, FSF activity, platelet clot retracting activity, ADP- and connective tissue-induced platelet aggregation and connective tissue - induced platelet ADP release. The effects of VPH became manifest or increased in intensity on incubation with the respective substrates prior to measurement of their activities. Inactivation of the VPH protease by DFP resulted in complete abolishment of the first four and partial inhibition of the last two of the above VPH activities.Administration of VPH to guinea pigs caused widespread hemorrhages, associated with moderate hypofibrinogenemia but normal platelet count, clotting time and clot retraction. DFP-treated VPH caused hemorrhage without hypofibrinogenemia.

Use of the Megathrombocyte to Demonstrate Thrombopoietin

1972 ◽  
Vol 28 (01) ◽  
pp. 024-030
Author(s):  
Weiner Marc ◽  
Karpatkin Simon
Keyword(s):  
Platelet Count ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Platelet Counts ◽  
Normal Platelet ◽  
Large Platelet ◽  
Platelet Number ◽  
Lag Period ◽  
Platelet Antibody

SummaryQuantitation of megathrombocyte (large platelet) number was used as an assay for the detection of a humorally-transmitted thrombopoietic stimulus, thrombopoietin. Donor guinea pigs were depleted of circulating platelets by the injection of rabbit anti-guinea pig platelet antibody. Plasma from these donor guinea pigs, when injected into recipient guinea pigs raised their platelet count 1.5 fold and their megathrombocyte number 2.7 fold when compared to plasma injected from donor guinea pigs with normal platelet counts. A lag period of 4 to 5 days preceded the rise in platelet count and megathrombocyte number.

Abnormal Prothrombin Consumption (Pc) In Bernard Soulier-Syndrome (BSS)

1981 ◽  
Author(s):  
J Pizzuto ◽  
M P Reyna ◽  
A González-Angulo ◽  
M R Morales ◽  
S Dorantes
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Aplastic Anemia ◽  
Normal Subjects ◽  
Procoagulant Activity ◽  
Normal Platelet ◽  
Abnormal Bleeding ◽  
Recalcification Time ◽  
Bernard Soulier Syndrome

The abnormal PC in BSS is a defect that has not been extensively studied to date. For this reason 4 patients with BSS who had normal platelet aggregation tests (except with bovine fibrinogen and with Ristocetin), but abnormal bleeding times and PC on different occasions, during which they showed variable thrombocytopenia, were studied. The PC was normal in only one case and in only one occasion, which was coincidental with a circulating platelet count that also approximated normal.The abnormal PC in the 4 cases was corrected when platelet substitute, or washed platelets from normal subjects or from patients with BSS were added. These same platelets also corrected the abnormal PC in cases of ITP or aplastic anemia, and shortened the recalcification time of platelet-poor plasmas from normal subjects and patients with specific plasma deficiencies (Factors V, VIII and XI).The above suggests that the abnormal PC in some cases of BSS may be due to the thrombocytopenia rather than to a defect in the procoagulant activity of the platelets in this syndrome.

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