Diagnostic Assessment of Patients with Inherited Mucocutaneous Hemorrhages (IMCH): Opening a Pandora Box?.

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.

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Cryptogenic oozers and bruisers

Hematology ◽

10.1182/hematology.2021000236 ◽

2021 ◽

Vol 2021 (1) ◽

pp. 85-91

Author(s):

Kristi J. Smock ◽

Karen A. Moser

Keyword(s):

Platelet Function ◽

Coagulation Factor ◽

Fibrin Clot ◽

Von Willebrand Disease ◽

Bleeding Disorders ◽

Diagnostic Challenge ◽

Primary Hemostasis ◽

Platelet Function Disorders ◽

Number Of Patients ◽

Von Willebrand

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.

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Tranexamic Acid Inhibits Fibrinolysis, Shortens the Bleeding Time and Improves Platelet Function in Patients with Chronic Renal Failure

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614370 ◽

1999 ◽

Vol 82 (10) ◽

pp. 1250-1254 ◽

Cited By ~ 23

Author(s):

Olga Panes ◽

Blanca Muñoz ◽

Edgar Pais ◽

Rodrigo Tagle ◽

Fernando González ◽

...

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Platelet Aggregation ◽

Tranexamic Acid ◽

Platelet Function ◽

Bleeding Time ◽

Degradation Products ◽

Severe Disease ◽

Plasmin Activity ◽

Primary Hemostasis

Summary Background: A defect in platelet function is the main determinant of the prolonged bleeding time in chronic renal failure (CRF). We previously reported a significant correlation between platelet abnormalities and elevated plasma markers of plasmin and thrombin generation. Our aim was to explore the effect of inhibiting both plasmin action with tranexamic acid (TA) and thrombin production with low molecular weight heparin (LMWH), on the bleeding time (BT) and platelet function in patients with CRF. Methods: 37 patients with CRF (mean creatinine 8.6 ± 4.4 mg/dl) under conservative treatment, with prolonged BT, entered this study and received TA during 6 days, with (n = 24) and without LMWH (n = 13). BT, platelet aggregation/secretion, platelet granule contents, von Willebrand factor and parameters of coagulation and fibrinolysis were recorded before and at the end of treatment. Results: The BT was shortened in 26/37 (67%) patients. This effect was associated with significant improvement of platelet aggregation and secretion, with decrease to a normal range of fibrin/fibrinogen degradation products, mild increase in plasmin-antiplasmin complexes and pronounced reduction of circulating plasminogen. No differences were seen among patients with or without LMWH. No serious side effects or complications were observed. Interpretation: These findings indicate that the activation of fibrinolysis plays a significant role in the defect of primary hemostasis in patients with CRF. Inhibition of plasmin activity with TA shortens the BT and improves platelet function in the majority of patients with severe disease.

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Platelet Antagonists

Fibrinolytic and Antithrombotic Therapy ◽

10.1093/oso/9780195155648.003.0035 ◽

2006 ◽

Author(s):

Richard C. Becker ◽

Frederick A. Spencer

Keyword(s):

Platelet Function ◽

Bleeding Time ◽

Cell Function ◽

Light Transmission ◽

Platelet Rich Plasma ◽

Blood Flow Rate ◽

Von Willebrand Disease ◽

Platelet Glycoprotein ◽

Primary Hemostasis ◽

Monitoring Tools

Platelet antagonists play an important role in both primary and secondary prevention of atherothrombotic events. Despite their proven benefit, individual response (and protection) varies considerably, emphasizing the importance of developing monitoring tools (tested prospectively in clinical trials) that can better determine the degree of platelet inhibition that is both safe and effective. Platelet function studies were developed originally for the evaluation of patients with unexplained bleeding and have contributed greatly to the understanding, diagnosis, and management of hereditary abnormalities such as von Willebrand disease and Glanzmann’s thrombasthenia (platelet glycoprotein [GP] IIb/IIIa receptor deficiency). Although conventional platelet function studies (turbidimetric aggregometry) have technical limitations that preclude their routine use for gauging antithrombotic therapy, they may provide guidance when hemorrhagic complications arise and in determining pretreatment risk in individuals suspected of having an intrinsic platelet abnormality. The bleeding time, considered an indicator of primary hemostasis (platelet plug formation), is defined as the time between making a small standardized skin incision and the precise moment when bleeding stops. The test is performed with a template, through which the medial surface of the forearm is incised under 40 mmHg standard pressure. A normal bleeding time is between 6 and 10 minutes. Although considered a “standardized” test of platelet function, the bleeding time can be influenced by a variety of factors, including platelet count, qualitative abnormalities, and features intrinsic to the blood vessel wall (George and Shattil, 1991). Platelet adhesion is the initiating step in primary hemostasis. Although platelet binding is an important component of this process, there are many others, including blood flow rate, endothelial cell function, adhesive proteins, and the subendothelial matrix. The original test used for assessing adhesion, platelet retention, was based on adherence to glass bead columns. The current laboratory evaluation of platelet function is based predominantly on turbidimetric platelet aggregometry (also known as light transmission aggregometry). This test is performed by preparing platelet-rich plasma (with platelet-poor plasma as a control) and eliciting an aggregation response with adenosine diphosphate, epinephrine, collagen, arachidonic acid, and ristocetin (Born, 1962).

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Phenotypic approaches to gene mapping in platelet function disorders

Hämostaseologie ◽

10.1055/s-0037-1617145 ◽

2010 ◽

Vol 30 (01) ◽

pp. 29-38 ◽

Cited By ~ 34

Author(s):

S. Watson ◽

M. Daly ◽

B. Dawood ◽

P. Gissen ◽

M. Makris ◽

...

Keyword(s):

Platelet Function ◽

Genetic Disorders ◽

Complex Trait ◽

Short Review ◽

Standard Test ◽

Normal Platelet ◽

Platelet Function Disorders ◽

Platelet Number ◽

Targeted Gene Sequencing

SummaryPlatelet number or function disorders cause a range of bleeding symptoms from mild to severe. Patients with platelet dysfunction but normal platelet number are the most prevalent and typically have mild bleeding symptoms. The study of this group of patients is particularly difficult because of the lack of a gold-standard test of platelet function and the variable penetrance of the bleeding phenotype among affected individuals.The purpose of this short review is to discuss the way in which this group of patients can be investigated through platelet phenotyping in combination with targeted gene sequencing. This approach has been used recently to identify patients with mutations in key platelet activation receptors, namely those for ADP, collagen and thromboxane A2 (TxA2). One interesting finding from this work is that for some patients, mild bleeding is associated with heterozygous mutations in platelet proteins that are co-inherited with other genetic disorders of haemostasis such as type 1 von Willebrand‘s disease. Thus, the phenotype of mild bleeding may be multifactorial in some patients and may be considered to be a complex trait.

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Coagulation Abnormalities and Hemostatic Surgical Outcomes in 142 Patients with Noonan Syndrome

Blood ◽

10.1182/blood.v128.22.1417.1417 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1417-1417

Author(s):

Juliana Perez Botero ◽

Thanh Ho ◽

Vilmarie Rodriguez ◽

Shaquila P Khan ◽

Rajiv K. Pruthi ◽

...

Keyword(s):

Developmental Delay ◽

Platelet Function ◽

Surgical Procedures ◽

Surgical Outcomes ◽

Noonan Syndrome ◽

Coagulation Factor ◽

Platelet Dysfunction ◽

Coagulation Abnormalities ◽

Coagulation Defects

Abstract Background: Noonan syndrome, characterized by dysmorphic facies, webbed neck, short stature, chest deformity, developmental delay and congenital heart defects, occurs as a result of mutations affecting the RAS-MAPK signaling pathway. A wide range of coagulation abnormalities are observed in these patients including: thrombocytopenia, platelet dysfunction and coagulation factor deficiencies. Screening for coagulation defects is recommended in childhood and especially prior to surgical procedures. Data available is limited and the extent of the hemostatic evaluation needed is not clearly defined. We carried out this study to outline the spectrum of coagulation abnormalities seen in patients with Noonan syndrome and their impact on surgical outcomes. Methods: In this retrospective cohort study, the electronic medical record system was queried for patients with Noonan syndrome seen at Mayo Clinic between 2000 and 2016. A detailed chart review was undertaken. Results i) Phenotypic correlates: 142 patients (58% male) met our study criteria, median age 21 years (range 14 days to 68 years). The referral specialty for initial evaluation was: cardiology 69 (49%), endocrinology 10 (7%), urology 10 (7%), neurology 8 (6%), pulmonary 6 (4%), orthopedic surgery 3 (2%), gastroenterology 2 (1%), psychiatry 2 (1%) and other specialties 4 (3%). Ten patients (7%) were referred for developmental delay, 13 (9%) for dysmorphism and 4 (3%) after having a family member diagnosed with Noonan syndrome. One patient (1%) presented with hematochezia. Twenty-seven (52%) of the 52 patients screened with genetic testing had a Noonan-associated gene defect. Bleeding was reported by 22 patients (15%) with a median International Society on Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH-BAT) score of 2 (range 1-8). Of those tested, 11/121 (9%) patients had thrombocytopenia (platelets < 150 x 10^9/L). Screening coagulation tests were done in 58 (41%) patients, and included PT/aPTT in 43 (74%) and extended coagulation panels (including platelet function studies) in 15 (26%). Of the 22 patients with history of bleeding, 20 (90%) had screening coagulation testing. Twenty-two (38%) of patients screened had one or more coagulation laboratory abnormality. Ten (66%) patients with clinically suspected platelet dysfunction had normal platelet function analyzer (PFA)-100 testing and normal light transmission aggregometry, while 5 (33%) had decreased platelet aggregation with epinephrine. Four patients (7%) (including 2 siblings) had low vWF levels consistent with type 1 vWD, 9 (16%) had mild clotting factor deficiencies ( FIX- 3, FXII-2 and multiple clotting factors-5) and 4 (7%) had a prolonged baseline PT and/or aPTT without additional coagulation factor assessment (Table 1). Thirteen patients (9%) had both a bleeding phenotype and abnormal coagulation laboratory results. ii) Surgical outcomes: A total of 274 surgical procedures were performed in 89 patients (63%). These included: cardiac 118 (43%), orthopedic 30 (11%), ENT 27 (10%), neurosurgical 26 (10%), abdominal 17 (6%), urologic 17 (6%), gynecologic 12 (4%) thoracic 8 (3%), ophthalmologic 7 (3%), plastic surgery 5 (2%), maxillofacial 4 (1%) and lymph node dissection 3 (1%). Platelets were utilized in 26 procedures (10%), fresh frozen plasma in 19 (7%) and cryoprecipitate in 7 (3%). Two procedures were performed in patients with type 1 vWD using vWF concentrates. Abnormal intra or postoperative bleeding was seen in 5/274 procedures (1.8%) performed in 4 patients. One patient had a known functional platelet disorder, one had normal PT and aPTT and two were not screened for coagulation defects. Bleeding was managed with transfusional supportive care in 3 (60%) surgical cases, while in 2 (40%) cases patients required re-intervention to achieve surgical hemostasis (bleeding from femoral access site and pacemaker pocket hematoma). There was no mortality related to the excess perioperative bleeding. Conclusion: Varying hemostatic abnormalities are seen in patients with Noonan syndrome, ranging from thrombocytopenia to multiple coagulation factor deficiencies. Frank bleeding manifestations however are uncommon and when present are usually mild. Clinical evaluation focused on the bleeding history and basic coagulation screening allows for successful perioperative hemostatic support and good surgical outcomes. Disclosures No relevant conflicts of interest to declare.

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Is my patient a bleeder? A diagnostic framework for mild bleeding disorders

Hematology ◽

10.1182/asheducation.v2012.1.466.3798741 ◽

2012 ◽

Vol 2012 (1) ◽

pp. 466-474 ◽

Cited By ~ 36

Author(s):

Teresa Quiroga ◽

Diego Mezzano

Keyword(s):

Screening Tests ◽

Laboratory Evaluation ◽

Bleeding Disorders ◽

Clotting Factors ◽

Primary Hemostasis ◽

Platelet Function Disorders ◽

Diagnostic Framework ◽

Wall Interaction ◽

Mild Bleeding Disorders

Abstract Congenital mild bleeding disorders (MBDs) are very prevalent and are the source of frequent diagnostic problems. Most MBDs are categorized as disorders of primary hemostasis (ie, type 1 VWD and platelet function disorders), but mild or moderate deficiencies of clotting factors and some rare hyperfibrinolytic disorders are also included. These patients have abnormal bleeding from the skin and mucous membranes, menorrhagia, and disproportionate hemorrhages after trauma, invasive procedures, and surgery. This review addresses the main problems that physicians and hemostasis laboratories confront with the diagnosis of these patients, including: discerning normal/appropriate from pathological bleeding, the role and yield of screening tests, the lack of distinctive bleeding pattern among the different diseases, the inherent difficulties in the diagnosis of type 1 VWD and the most common platelet functional disorders, improvements in assays to measure platelet aggregation and secretion, and the evidence that most of the patients with MBDs end up without a definite diagnosis after exhaustive and repeated laboratory testing. Much research is needed to determine the pathogenesis of bleeding in MBD patients. Better standardization of current laboratory assays, progress in the knowledge of fibrinolytic mechanisms and their laboratory evaluation, and new understanding of the factors contributing to platelet-vessel wall interaction, along with the corresponding development of laboratory tools, should improve our capacity to diagnose a greater proportion of patients with MBDs.

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Risk and Management of Intracerebral Hemorrhage in Patients with Bleeding Disorders

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0041-1740566 ◽

2022 ◽

Author(s):

Akbar Dorgalaleh ◽

Yadolah Farshi ◽

Kamand Haeri ◽

Omid Baradarian Ghanbari ◽

Abbas Ahmadi

Keyword(s):

Risk Factors ◽

Intracerebral Hemorrhage ◽

Platelet Function ◽

Hemophilia A ◽

Coagulation Factor ◽

Von Willebrand Disease ◽

Vacuum Extraction ◽

Bleeding Disorders ◽

Platelet Function Disorders ◽

Von Willebrand

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.

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Platelet Function Disorders in Bleeding Patients without Other Coagulopathies

Blood ◽

10.1182/blood.v126.23.4650.4650 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4650-4650

Author(s):

Francine R. Dembitzer ◽

Ellinor I.B. Peerschke ◽

Caroline Cromwell ◽

Xiaofei Zhang ◽

Louis M. Aledort

Keyword(s):

Platelet Aggregation ◽

Board Of Directors ◽

Platelet Function ◽

Coagulation Factor ◽

Clinical History ◽

Study Cohort ◽

Advisory Committees ◽

Normal Platelet ◽

Platelet Function Disorders ◽

Age Range

Abstract Introduction: We present a series of 105 patients referred for hematologic consultation to evaluate a clinical bleeding disorder. Little is known regarding the prevalence of non-genetic qualitative platelet disorders and which of these might respond to desmopressin. Methods: Patients were assessed over a two-year period, from December 2011 through December 2013. Patients, who were found to have neither von Willebrand's disease nor coagulation factor deficiencies, nor quantitative platelet defects, were tested for platelet function abnormalities by PFA-100 (Dade Behring, Marburg, Germany) and platelet aggregation and secretion studies using lumi aggregation (Chrono-Log Corp., Havertown, PA, USA). Selected patients with abnormal platelet function were given a trial of intravenous desmopressin to determine efficacy, and platelet function studies were repeated 2 hours later. Results: Of the 105 referred patients (26 males, age range 15-83 years; 79 females, age range 21-86 years), 67 with either normal (n=43) or abnormal (n=24) PFA-100 results were not evaluated further based on their clinical history and presentation. 18 patients with abnormal PFA-100 results, consisting of Collagen/ADP, Collagen/Epinephrine, or both, had platelet aggregation and secretion studies performed. 16 of these patients had abnormal platelet aggregation and secretion studies, while 2 patients had normal studies. In addition, 20 patients with normal PFA-100 results underwent platelet aggregation and secretion studies. Of these, 17 had abnormal platelet aggregation and secretion predominantly in response to two or more weak agonists, including ADP, epinephrine and/or arachidonic acid. Only 3 of these 20 patients had normal platelet aggregation and secretion. Of the 16 patients with both abnormal PFA-100 and abnormal platelet aggregation and secretion tests, 11 underwent subsequent pre- and post- desmopressin platelet function testing. 7 of the 11 patients showed improvement or complete normalization of at least one PFA-100 parameter, i.e., either Collagen/ADP, Collagen/Epinephrine, or both. However, results of platelet aggregation and secretion tests remained unchanged, irrespective of PFA-100 results. Conclusions: In the present study, platelet aggregation and secretion studies in patients with no other coagulopathies revealed platelet function defects in approximately 30% of the study cohort. Platelet function defects were in response to weak agonists, including ADP, epinephrine, and/or arachidonic acid.Our data support the recent SCC ISTH recommendations against the use of PFA-100 for platelet function screening.We recommend that the hematologist carefully assess the bleeding history, and, if significant, pursue platelet aggregation and secretion studies to identify potential platelet function defects. Disclosures Aledort: Baxter Healthcare: Membership on an entity's Board of Directors or advisory committees, Other: DSMB Participation; Kedrion BioPharma: Consultancy, Membership on an entity's Board of Directors or advisory committees.

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Evaluation of the PFA-100® System in the Diagnosis and Therapeutic Monitoring of Patients with von Willebrand Disease

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614626 ◽

1999 ◽

Vol 82 (07) ◽

pp. 35-39 ◽

Cited By ~ 69

Author(s):

Augusto Federici ◽

Anna Lecchi ◽

Barbara Agati ◽

Rossana Lombardi ◽

Federica Stabile ◽

...

Keyword(s):

Platelet Function ◽

Bleeding Time ◽

Von Willebrand Disease ◽

Therapeutic Monitoring ◽

High Shear ◽

Before And After ◽

Type 3 ◽

Von Willebrand ◽

Willebrand Factor

SummaryWe have evaluated platelet function at high shear with the PFA-100® system in different subtypes of von Willebrand disease (vWD), before and after the intravenous infusions of desmopressin or a factor-VIII/von Willebrand factor (vWF) concentrate. Closure times with the PFA-100® system were determined for both the collagen/ADP and the collagen/epinephrine cartridges in 52 patients with vWD (9 type 1 “platelet normal”, 5 type 1 “platelet-discordant”, 8 type 1 “platelet-low”, 6 type 2A, 9 type 2B, 6 type 2M Vicenza, 6 type 3 and 3 acquired vWD) and 40 controls. Measurements were repeated 1 and 4 h after the i.v. infusion of desmopressin (0.3 μg/Kg) in 26 patients with types 1, type 2M Vicenza or type 2A vWD, or of a factorVIII/vWF concentrate (Alphanate HT, 60 U/Kg) in 4 patients with type 3 vWD. At all time points, vWF plasma levels and the bleeding time (Symplate II) were also determined. Baseline closure times were longer in vWD patients than in controls with both the collagen/ADP and the collagen/ epinephrine cartridges. The sensitivity of the PFA-100® system (88% and 87% with the two cartridges) was higher than that of the bleeding time (65%). Treatment with desmopressin normalized the closure times in patients with type 1 “platelet-normal” or type 2M Vicenza vWD, had no significant effects in patients with type 1 “platelet-low”, type 1 “platelet-discordant” or type 2A vWD. Infusion of a factorVIII/vWF concentrate in patients with type 3 vWD slightly shortened their prolonged closure times. In general, changes in PFA-100® were paralleled by shortenings of the bleeding times and increases in plasma vWF levels. The PFA-100® test reflects vWF-dependent platelet function under high shear stress and could be useful in the diagnosis and therapeutic monitoring of patients with vWD.

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Aspirin prolongation of the template bleeding time: influence of venostasis and direction of incision

Blood ◽

10.1182/blood.v60.5.1139.bloodjournal6051139 ◽

1982 ◽

Vol 60 (5) ◽

pp. 1139-1142

Author(s):

CH Jr Mielke

Keyword(s):

Platelet Aggregation ◽

Platelet Function ◽

Bleeding Time ◽

Bleeding Disorder ◽

Prostaglandin Biosynthesis ◽

Primary Hemostasis ◽

Normal Subject ◽

Normal Individuals ◽

Vertical Incision

The template bleeding time is a measure of platelet participation in primary hemostasis. Aspirin alters platelet function through interference with prostaglandin biosynthesis. In many individuals, aspirin will consistently prolong the bleeding time. Despite this observation, normal individuals rarely develop a bleeding disorder. This prompted us to investigate the influence of technical variables on the prolongation of the bleeding time by aspirin. Both direction of incision and venostasis influenced the prolongation of the bleeding time by aspirin. A horizontal incision with venostasis produced the most pronounced prolongation, while a vertical incision without venostasis didn't prolong the bleeding time despite the characteristic changes in platelet aggregation and release. These studies suggest that the influence of aspirin on the template bleeding time is dependent on technical variables and is minimal in the normal subject.

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