Congenital Hemorrhagic Disorders Research Articles

Totally extraperitoneal inguinal hernia repair in patients with hemophilia and von Willebrand disease. Prospective controlled study.

IntroductionLaparoscopic surgery is associated with several advantages. Surgical procedures in hemophilia or von Willebrand patients without replacement therapy (RT) to correct clotting factor deficiency may result in serious, life-threatening hemorrhagic episodes. Clotting factor concentrates improve hemostatic control but bleeding risk in major invasive procedures remains high.AimEvaluation of totally extraperitoneal inguinal hernia repair (TEP-IHR) in patients with congenital hemorrhagic disorders (H) and comparison with results for non-hemophiliacs (NH) with regard to bleeding, postoperative pain, hernia recurrence, surgery time, demand for painkillers, hospital stay and recovery time.Material and methodsThe prospective controlled trial included 67 consecutive male patients scheduled for TEP-IHR between January 2010 and December 2018. Surgery was performed in groups H (n = 22) and NH (n = 45). Full study inclusion criteria were met by 65 patients (22 and 43 in H and NH groups respectively). Follow-up was carried out on the 1st, 2nd, and 7th day and in the 1st and 3rd month postoperatively.ResultsTEP-IHR was successful for all patients. No life-threatening bleeding occurred and no patient required red blood cell transfusions or reoperation. No hernia recurrence was reported. No statistically significant differences were observed between the groups with regard to surgery duration, postoperative hematoma frequency and demand for painkillers. In the H group, pain intensity was significantly higher during the first postoperative month and hospitalization and recovery were significantly longer.ConclusionsTEP-IHR in hemophiliacs with RT is feasible and as effective for preventing hernia recurrence as in NH-patients. In hemophiliacs risk of bleeding complications and demand for painkillers are comparable to non-hemophiliacs although pain is more intense.

Oral Hygiene and Dentition Status in Patients with Congenital Hemorrhagic Disorders: A Comparative Study

Objective: To compare the status of oral hygiene and dentition in patients with congenital hemorrhagic disorders with their age-matched healthy counterparts. Also, the prevalence of fear of dentists/ dental treatment among these patients was assessed. Material and Methods: This study was performed on children and adults with von Willebrand disease (vWD), hemophilia (A or B), and healthy subjects. Oral health and dentition status was assessed using the simplified oral hygiene index (OHI-S), plaque index, and the decayed, missing, filled teeth (dmft/DMFT) index . One-way ANOVA test was employed to compare the oral hygiene and dentition status of subjects in the three groups. A p-value of 0.05). Higher OHI-S scores and a poor oral hygiene status was observed more in the hemophilia group than the vWD group and healthy controls. A total of 27.3% of the subjects in the vWD group, 18.2% of subjects in the hemophilia group, and no subjects in the healthy group had a fear of dentists or dental treatment . Conclusion: Subjects with vWD had a higher number of carious teeth when compared to the other groups. Poor oral hygiene status was observed in subjects with hemophilia.

Managing Patients with Low von Willebrand Factor Levels

Von Willebrand disease (VWD) is one of the most common congenital hemorrhagic disorders, yet it is often misdiagnosed or treated inappropriately.To

Laboratory diagnosis of clinically relevant platelet function disorders.

Inherited platelet function disorders (IPFDs) represent a significant fraction of congenital hemorrhagic disorders, and may be associated with bleeding of considerable severity. IPFDs may be difficult to diagnose and a preliminary accurate clinical examination and an objective evaluation of the severity of the bleeding history are mandatory. The laboratory investigation of IPFDs should follow a rational algorithm based on a streamlined panel of laboratory tests with subsequent steps of increasing levels of complexity. First screening tests include platelet count, peripheral blood smear, light transmission aggregometry, measurement of platelet granule content and release, and the expression of glycoproteins by flow cytometry. Several of these tests have been largely employed, and a few validated, for the diagnosis of IPFDs and some recent developments are discussed. Point-of-care tests may provide the advantage of rapidity and the possibility to study platelet function in whole blood, but further studies are required to clarify their potential diagnostic application. Genotyping is recommended for some conditions (genotype/phenotype correlations, forms associated with a high risk of developing hematologic malignancies) but, especially when carried out by next-generation sequencing (NGS) techniques, needs to be critically evaluated taking into account clinical and laboratory phenotypes.

Pulmonary embolism in congenital bleeding disorders: intriguing discrepancies among different clotting factors deficiencies.

Pulmonary embolism is a complication of deep vein thrombosis. It occurs in the population with a normal clotting mechanism, but it may also occur in patients with congenital bleeding conditions. Here, we report on all cases of pulmonary embolism in congenital hemorrhagic disorders. All reported cases of pulmonary embolism in congenital coagulation disorders have been gathered by a time-unlimited PubMed search. Cross-checking of the references listed at the end of the single papers was carried out to avoid omissions. Seventy-two patients had an objectively demonstrated pulmonary embolism. The event occurred in patients with fibrinogen, factor V, factor VIII (FVII), FVIII, FIX, and FXI deficiency, and in those with von Willebrand's disease. No embolism was reported in FII, factor X, and FXIII deficiency. Thirty were women and 28 were men, whereas in the remaining 14 cases, sex was not reported. Age varied from 6 to 81 years (mean age 34.3 years). The management varied from only supportive to the administration of unfractionated heparin, low-molecular-weight heparin, and anti-vitamin K medications, accompanied by adequate replacement therapy. Evolution was fair or good in the majority of cases, but there were 10 fatalities. Risk factors were present in 61 patients. The most frequent of these were replacement therapy (35 cases), surgery (34), and old age (13). Some patients had more than one risk factor. Eleven patients had no risk factors. There are discrepancies in the prevalence of pulmonary embolism among different clotting disorders. The conditions most frequently affected are FVII deficiency and fibrinogen defects. The significance of the findings is discussed.

Maladies hémorragiques congénitales : quel avenir pour les dérivés plasmatiques par rapport aux recombinants et aux produits sanguins labiles ?

Until 1990, congenital hemorrhagic disorders were treated by plasma-derived concentrates. The first recombinant drug, recombinant factor VIII was available after this date and few years later recombinant factor IX could also be proposed to patients. The evolution of market share in France was different between these two drugs: while recombinant factor VIII took a large place in hemophilia A treatment (85%), plasma-derived factor IX represent 50% of the French market. In the next years, the arrival of long-acting antihemophilic factors may lead to the dramatically reduce the amount of plasma-derived antihemophilic factors used to treat hemophilia. For rare bleeding coagulation disorders, plasma-derived concentrates are still widely used, while they are the only concentrates available in most diseases. This situation is unlikely to evolve significantly in the next years.

Management of Kidney Transplantation in a Factor VII-Deficient Patient: Case Report

Transplantation in patients with congenital bleeding disorders is a challenge requiring an integrated approach of various specialists. Renal transplantation, the most frequent type of solid organ transplantation, is rarely performed in individuals with congenital hemorrhagic disorders. We performed a renal transplantation in a 53-year-old man with end-stage renal disease and congenital coagulation factor VII deficiency, a rare bleeding disorder with a peculiar clinical picture requiring replacement therapy in surgical interventions. Perioperative bleeding was successfully prevented by administration of recombinant activated factor VII. Treatment schedule, administration rate, and long-term follow-up are reported in detail. Our report confirmed the feasibility and safety of recombinant activated factor VII in major surgical procedures like solid organ transplantations. Success requires evaluation of doses and therapeutic schedules as well as a multidisciplinary approach.

Whole blood rotation thromboelastometry (ROTEM®) in nine severe factor V deficient patients and evaluation of the role of intraplatelets factor V

Severe factor V (FV) deficiency (parahaemophilia) is a rare congenital hemorrhagic disorder characterized by very low or undetectable plasma FV levels and bleeding phenotype ranging from mild to severe. We evaluated whole blood (WB) rotation thromboelastometry (ROTEM) in parahaemophilia patients and the contribution of intraplatelets FV, if any, to clot formation. Standard ROTEM(®) assays were performed in WB from nine parahaemophilia patients and 50 healthy controls. In addition, platelets poor plasma from one parahaemophilia patient (PPP-Pt) or normal subjects (PPP-N) was reconstituted with washed platelets obtained either from one patient with parahaemophilia (Plts-Pt) or normal subjects (Plts-N) and ROTEM assays were performed in platelets rich plasma (PRP) samples. There was a prolongation of the WB clotting time (CT) in all assays in patients as compared with controls. However, maximum clot firmness (MCF) was similar in patients and controls. ROTEM in PPP-Pt showed both a prolongation of CT and a reduction of MCF as compared with PPP-N. The addition of either Plts-Pt or Plts-N to PPP-Pt resulted in similar increase in MCF and a decrease of CT which was more evident for PPP-Pt + Plts-N than PPP-Pt + Plts-Pt. In contrast, the addition of Plts-Pt or Plts-N to PPP-N had superimposable effects on both CT and MCF. In parahaemophilia patients, WB ROTEM(®) presents mainly with prolongation of CT and no relevant effect on MCF. Residual intraplatelets FV in parahaemophilia contributes significantly to thrombin generation as shown in artificially reconstituted PRP models.

Rare and Unusual Bleeding Manifestations in Congenital Bleeding Disorders

Epistaxis, superficial and deep hematomas, hemarthrosis, gastrointestinal bleeding, hematuria represent the most frequent hemorrhagic events in congenital coagulation disorders. Occasionally, bleeding manifestations occur in unusual sites or are peculiar. A clotting defect may alter the clinical aspect of skin conditions or infections (hemorrhagic scabies or varicella). Hemobilia may occur as a complication of transjugular liver biopsy in hemophilia or Bernard-Soulier syndrome. Hemarthrosis of small joints of feet and hands occur in patients with hemophilia treated with protease inhibitors. Intramedullary hematomas of long bones have been described in α2-plasmin inhibitor or fibrinogen deficiencies. Spleen fracture with consequent hemoperitoneum has been reported in patients with fibrinogen deficiency. Rectus muscle sheath hematoma may occur in patients with factor VII (FVII)or FX deficiency. Acute or subacute intestinal obstruction may be caused by intramural wall hematomas in hemophilia and von Willebrand (vW)-disease. Physicians should always keep in mind that a congenital hemorrhagic disorder may cause bleeding in any tissue of the body and therefore alter the normal clinical features of a given disease.

SINGLE-CENTER EXPERIENCE: Use of Recombinant Factor VIIa for Acute Life-Threatening Bleeding in Children without Congenital Hemorrhagic Disorder

Coagulopathy is an important cause of mortality in critically ill children. Traditional therapies to correct coagulopathy lead to great time delays and cause fluid overload in patients. The authors report the effectiveness and safety of the activated recombinant factor VII (rFVIIa) administration in a series of 13 nonhemophiliac children with acute, life-threatening bleeding. In this retrospective study, the records of the patients who were not diagnosed with congenital hemorrhagic disorder and were administered rFVIIa due to any other reason in Ege University Faculty of Medicine, Department of Pediatrics, between February 2002 and February 2007 were reviewed retrospectively. Thirteen nonhemophiliac patients with acute life-threatening bleeding and ages ranging from 2 days to 15 years received rFVIIa over a 5-year period. Three patients were diagnosed with hemaphagocytic lymphohistiocytosis, 4 with prematurity, sepsis, and disseminated intravascular coagulation (DIC), 5 with sepsis, multiple organ dysfunction syndrome, and DIC, and 1 with acute liver failure. Severe bleeding resulted from pulmonary (n = 3), lower gastrointestinal system (n = 2), esophagus varices (n = 1), pulmonary and gastrointestinal system (n = 4), pulmonary, gastrointestinal system, and intracranial hemorrhage (n = 1), and gastrointestinal system and intracranial hemorrhage (n = 2). Median frequency of rFVIIa administration was 3 per patient (range 2–15) and median dose of rFVIIa was 90 μg/kg, ranging from 60 to 135 μg/kg each administration. All of the patients were given fresh frozen plasma and if necessary platelet transfusion (n = 10) or fibrinogen concentrate (n = 3) before administration of rFVIIa. In 6 patients, lack of success to control bleeding by conventional methods was the only cause to start rFVIIa. In 7 patients, the need for volume restriction was also a significant contributing factor in deciding to start rFVIIa. Median PT was 32.9 s (range: 19–65) before rFVIIa administration and it was decreased to 11.6 s (range: 10.7–12.8), 2–3 h after rFVIIa infusion. Bleeding was stopped completely in 10 patients at least for 24 h and decreased in 3 patients 30–45 min after rFVIIa administration. Two patients had thrombotic complications attributed to rFVIIa administration. No other complication was observed in the other patients. In this retrospective study, rFVIIa was found to be effective at controlling severe hemorrhagic symptoms of different etiologies in children without congenital hemorrhagic disorder. In addition to the rapid control of bleeding, administration of this agent improved fluid balance and led to a reduction in blood product requirements in critically ill children. However, survival was still poor (23%), and 2/13 (15.4%) patients developed venous and arterial thrombosis within 3 h of treatment. The authors emphasize that in acquired, acute life-threatening bleeding, simultaneous administration of rFVIIa with conventional treatment may contribute to patient survival. However, the risk of thromboembolism should be considered before this treatment is given.

A new case of combined factor V and factor VIII deficiency further suggests that the LMAN1 M1T mutation is a frequent cause in Italian patients

Combined factor V and factor VIII deficiency (F5F8D) is an extremely rare worldwide congenital hemorrhagic disorder that is more prevalent in the Mediterranean area. We report the clinical presentations and the identification of a LMAN1 mutation in a 3-year-old Italian boy who was diagnosed with F5F8D. The mutation identified (M1T) has already been found in several Italian patients. Since the LMAN1 M1T mutation has been identified in most patients with F5F8D, we suggest that the search for this mutation should be the first step in the molecular characterization of patients from an Italian ethnic background.

Perioperative Management of a Heterozygous Carrier of Glanzmann’s Thrombasthenia Submitted to Coronary Artery Bypass Grafting With Cardiopulmonary Bypass

Glanzmann's thrombasthenia is a congenital hemorrhagic disorder transmitted as an autosomal recessive trait and characterized by altered production and/or assembly of the platelet membrane glycoprotein IIb/IIIa receptor. We describe the perioperative management of a heterozygous carrier of Glanzmann's thrombasthenia submitted to cardiac surgery with cardiopulmonary bypass and the case was complicated by early excessive postoperative bleeding.

Dental procedures in adult patients with hereditary bleeding disorders: 10 years experience in three Italian Hemophilia Centers

Excessive bleeding after dental procedures are one of the most frequent complications occurring in patients with hereditary bleeding disorders. In this retrospective study we collected data from 10 years of experience in the oral care of patients with congenital haemorrhagic disorders in three Italian Hemophilia Centers. Between 1993 and 2003, 247 patients with inherited bleeding disorders underwent 534 dental procedures including 133 periodontal treatments, 41 conservative dentistry procedures, 72 endodontic treatments and 288 oral surgery procedures. We recorded 10 bleeding complications (1.9%), most of which occurred in patients with severe/moderate haemophilia A undergoing multiple dental extractions. Thus, our protocol of management of patients with hereditary bleeding tendency undergoing oral treatment or surgery has been shown to be effective in preventing haemorrhagic complications.

Managing the bleeding patient.

1. George A Fritsma, MS MT(ASCP)[⇑][1] 1. is in the Department of Pathology, UAB Coagulation Service Coordinator at the University of Alabama at Birmingham, Birmingham AL 1. Address for correspondence: George A Fritsma MS MT (ASCP), Department of Pathology, 619 South 19th Street, West Pavilion, P230, University of Alabama at Birmingham, Birmingham AL 35249. gfritsma{at}path.uab.edu. Website: The reader will be able to: 1. distinguish between anatomic and systemic hemorrhage. 2. distinguish between acquired and congenital hemorrhage. 3. select hemostatic laboratory tests that may be used to establish the presence of a hemostatic disorder. 4. identify hemostatic laboratory tests for use in pinpointing the cause of hemorrhage. 5. interpret the laboratory test profile results used to establish the presence of disseminated intravascular coagulation. 6. interpret the laboratory test profile results used to establish the presence of von Willebrand disease. 7. select single coagulation factor assays. 8. describe how to perform and interpret mixing studies. 9. determine the presence of a coagulation inhibitor. 10. select the appropriate coagulation factor concentrate therapy to treat hemorrhagic disorders. 11. calculate the correct dosage of coagulation factor concentrate to appropriately treat hemorrhagic disorders. 12. assess the dosage adequacy of the coagulation factor concentrate used to treat hemorrhagic disorders. 13. detail the selection and dosage of factor concentrates for von Willebrand disease, hemophilia, and hemophilia with the presence of an inhibitor. The acute care hemostasis laboratory must be equipped to manage both acute and chronic hemorrhage. Hemorrhage is defined as bleeding that can be arrested only by special interventions such as pressure, elevation, ice, cauterization, ligation, or therapy.1 Therapy may include non-biologic drugs such as DDAVP and Amicar, and coagulation concentrates in various forms. Hemorrhage may be local or general, anatomic or systemic, acquired or congenital . To establish the cause for a hemorrhagic event, the clinician first completes a history and physical examination, and then follows up with diagnostic laboratory tests.2 LOCAL VERSUS GENERAL HEMORRHAGE Most bleeding is local. Hemorrhage from a single location signals a trauma, tissue necrosis, or a blood vessel defect. A surgical site may bleed because of an inadequately ligated or cauterized vessel. Local bleeding seldom implies a coagulopathy. Bleeding is classified as general when it is excessive or when it originates from two or more sites (Table 1). Menorrhagia, hematemesis, epistaxis, bleeding from the gums, or bleeds into body cavities are signs of a hemostatic deficiency. Whenever such a coagulopathy is suspected, a careful workup involving hemostasis laboratory tests is essential.3,4 ACQUIRED VERSUS CONGENITAL HEMORRHAGIC DISORDERS Bleeding that first occurs in adulthood, is associated with a specific disorder (Table 2), and is not seen in kindred, implies an acquired hemorrhagic condition. When an adult patient presents with general hemorrhage, the physician first looks for an underlying disease, and then orders a hemostasis laboratory test profile.5 Congenital coagulopathies are uncommon, occurring in approximately one in 800 individuals,… ABBREVIATIONS: PT = prothrombin time; PTT = partial thromboplastin time. The reader will be able to: 1. distinguish between anatomic and systemic hemorrhage. 2. distinguish between acquired and congenital hemorrhage. 3. select hemostatic laboratory tests that may be used to establish the presence of a hemostatic disorder. 4. identify hemostatic laboratory tests for use in pinpointing the cause of hemorrhage. 5. interpret the laboratory test profile results used to establish the presence of disseminated intravascular coagulation. 6. interpret the laboratory test profile results used to establish the presence of von Willebrand disease. 7. select single coagulation factor assays. 8. describe how to perform and interpret mixing studies. 9. determine the presence of a coagulation inhibitor. 10. select the appropriate coagulation factor concentrate therapy to treat hemorrhagic disorders. 11. calculate the correct dosage of coagulation factor concentrate to appropriately treat hemorrhagic disorders. 12. assess the dosage adequacy of the coagulation factor concentrate used to treat hemorrhagic disorders. 13. detail the selection and dosage of factor concentrates for von Willebrand disease, hemophilia, and hemophilia with the presence of an inhibitor. [1]: #corresp-1

PERAWATAN GIGI DAN MULUT PENDERITA HEMOFILIA

Haemophilia is a congenital haemorrhagic disorders passed down by the x linked recessive, divided into two: Haemophilia A caused by deficiency of factor VIII and Haemophilia B caused by deficiency of factor IX. Since spontaneous bleeding or bleeding after dental treatment can cause severe or even fatal complication, people with haemophilia or congenital bleeding tendencies are priority group for dental and oral preventive health care. Maintenance of a healthy mouth and prevention of dental problem is thus of great importance, not only for quality of life and nutrition but also to avoid complications of surgery.

Congenital Hemorrhagic Disorders: New Insights into the Pathophysiology and Treatment of Hemophilia

The diagnostic and treatment strategies related to hemophilia are rapidly evolving. This article focuses on some of the issues of importance. Diagnostic advances in molecular genetics are reviewed by Dr. Ginsburg in Section I, including the current state of knowledge regarding the mutations responsible for hemophilia, with reference to the potential clinical applications of DNA diagnosis and prenatal testing. Within the area of new therapeutic approaches in hemophilia, recombinant factor VIII and factor IX concentrates, their use and availability are addressed by Dr. Lusher in Section II as well as the use of so-called "primary prophylaxis" with the aim of decreasing long-term hemophilia athropathy. The use of radionuclide synovectomy as replacement for more invasive methods is also reviewed. Various approaches to the ongoing challenge of the management of hemophilia patients with inhibitors against factor VIII and factor IX are reviewed by Dr. Hedner in Section III, including the principles for immune tolerance induction and the use of recombinant factor VIIa to induce hemostasis in bleeding patients with inhibitors. In Section IV, gene therapy in hemophilia is reviewed by Dr. High, who focuses on recent developments in the rapidly moving field of gene therapy for hemophilia. Three phase I trials of gene therapy for hemophilia were initiated in 1999, and additional proposed trials are currently in the regulatory review process. Certain aspects of the pathophysiology of hemophilia make it an attractive model for a gene-based approach to treatment. These include latitude in choice of target tissue, a wide therapeutic window, the availability of small and large animal models of the disease, and the ease of determining therapeutic efficacy. Since there is very little published information regarding the ongoing trials, this section reviews the approaches being used, the published pre-clinical data, and considerations affecting clinical trial design in hemophilia gene therapy.

Congenital Hemorrhagic Disorders: New Insights into the Pathophysiology and Treatment of Hemophilia

AbstractThe diagnostic and treatment strategies related to hemophilia are rapidly evolving. This article focuses on some of the issues of importance. Diagnostic advances in molecular genetics are reviewed by Dr. Ginsburg in Section I, including the current state of knowledge regarding the mutations responsible for hemophilia, with reference to the potential clinical applications of DNA diagnosis and prenatal testing.Within the area of new therapeutic approaches in hemophilia, recombinant factor VIII and factor IX concentrates, their use and availability are addressed by Dr. Lusher in Section II as well as the use of so-called “primary prophylaxis” with the aim of decreasing long-term hemophilia athropathy. The use of radionuclide synovectomy as replacement for more invasive methods is also reviewed.Various approaches to the ongoing challenge of the management of hemophilia patients with inhibitors against factor VIII and factor IX are reviewed by Dr. Hedner in Section III, including the principles for immune tolerance induction and the use of recombinant factor VIIa to induce hemostasis in bleeding patients with inhibitors.In Section IV, gene therapy in hemophilia is reviewed by Dr. High, who focuses on recent developments in the rapidly moving field of gene therapy for hemophilia. Three phase I trials of gene therapy for hemophilia were initiated in 1999, and additional proposed trials are currently in the regulatory review process. Certain aspects of the pathophysiology of hemophilia make it an attractive model for a gene-based approach to treatment. These include latitude in choice of target tissue, a wide therapeutic window, the availability of small and large animal models of the disease, and the ease of determining therapeutic efficacy. Since there is very little published information regarding the ongoing trials, this section reviews the approaches being used, the published pre-clinical data, and considerations affecting clinical trial design in hemophilia gene therapy.

Congenital Hemorrhagic Disorders: New Insights into the Pathophysiology and Treatment of Hemophilia

The diagnostic and treatment strategies related to hemophilia are rapidly evolving. This article focuses on some of the issues of importance. Diagnostic advances in molecular genetics are reviewed by Dr. Ginsburg in Section I, including the current state of knowledge regarding the mutations responsible for hemophilia, with reference to the potential clinical applications of DNA diagnosis and prenatal testing.Within the area of new therapeutic approaches in hemophilia, recombinant factor VIII and factor IX concentrates, their use and availability are addressed by Dr. Lusher in Section II as well as the use of so-called “primary prophylaxis” with the aim of decreasing long-term hemophilia athropathy. The use of radionuclide synovectomy as replacement for more invasive methods is also reviewed.Various approaches to the ongoing challenge of the management of hemophilia patients with inhibitors against factor VIII and factor IX are reviewed by Dr. Hedner in Section III, including the principles for immune tolerance induction and the use of recombinant factor VIIa to induce hemostasis in bleeding patients with inhibitors.In Section IV, gene therapy in hemophilia is reviewed by Dr. High, who focuses on recent developments in the rapidly moving field of gene therapy for hemophilia. Three phase I trials of gene therapy for hemophilia were initiated in 1999, and additional proposed trials are currently in the regulatory review process. Certain aspects of the pathophysiology of hemophilia make it an attractive model for a gene-based approach to treatment. These include latitude in choice of target tissue, a wide therapeutic window, the availability of small and large animal models of the disease, and the ease of determining therapeutic efficacy. Since there is very little published information regarding the ongoing trials, this section reviews the approaches being used, the published pre-clinical data, and considerations affecting clinical trial design in hemophilia gene therapy.

Glanzmann's Thrombasthenia Type II in a Saudi Child: A Case Report

Glanzmann's Thrombasthenia Type II in a Saudi Child: A Case Report

Bernard-Soulier Syndrome: Whole Blood Diagnostic Assays of Platelets

Diagnosing Bernard-Soulier syndrome (BSS), a congenital hemorrhagic disorder of blood platelets, is complicated by the difficulty of separating the giant platelets from other blood cells to allow studies of platelet function and structure. We report on the use of three whole blood assays for diagnosing BSS. Whole blood platelet aggregation responses studied with an electrical impedance aggregometer were equivalent to those more laboriously obtained by using platelet-rich plasma prepared by unit gravity sedimentation and studied with an optical light transmittance aggregometer. Platelet aggregation responses were normal with adenosine diphosphate or collagen stimulation but absent with ristocetin or bovine plasma stimulation. Whole blood radioimmunoassay of platelet glycoprotein (GP) expression was performed by using iodinated murine monoclonal antibodies HP1-1D (anti-GP IIb/IIIa) and 6D1 (anti-GP Ib). After incubation with citrated whole blood, centrifugation was used to separate cell-bound antibody that was quantitated with a gamma counter. The patient's whole blood had a normal level of cell-bound GP IIb/IIIa but a substantially reduced level of cell-bound GP Ib (5% of normal mean). Whole blood smear immunocytochemical staining with monoclonal antibodies and qualitative analysis by light microscopy revealed a considerable reduction of GP Ib expression by the patient's giant platelets, whereas GP IIb/IIIa expression was normal. These data helped establish the diagnosis of BSS. We conclude that these three relatively simple assays of platelets in whole blood should be of particular value in the clinical laboratory differential diagnosis of patients with congenital thrombocytopenias and giant platelet syndromes.