Hemostasis Primer

Hemostasis Primer. An essential primer for understanding the role of topical hemostats surgical sealants and adhesives for maintaining hemostasis A wide variety of topical hemostats are approved as adjunctive therapies in the maintenance of hemostasis during surgical procedures in which conventional methods are insufficient or not practical Author Michael Gabay Bradley A BoucherCited by Publish Year 2013.

Hemostasis is the mechanism that leads to cessation of bleeding from a blood vessel It is a process that involves multiple interlinked steps This cascade culminates into the formation of a “plug” that closes up the damaged site of the blood vessel controlling the bleeding It begins with trauma to the lining of the blood vessel Stages.

Current Understanding of Hemostasis

There are four phases involved in primary hemostasis vasoconstriction platelet adhesion platelet activation and platelet aggregation Secondary hemostasis – formation of the final stable fibrin clot which is triggered by the complex series of events known as the proteolytic coagulation cascade.

Hemostasis Part 1 Primary and Secondary Hemostasis Med

IntroductionSequence of EventsInhibitorsClinical SignsSample CollectionTestsDisordersDefinition Primary hemostasis is defined as the formation of the primary platelet plug This serves to plug off small injuries especially in microvessels (< 100 μm) in mucosal tissues (respiratory gastrointestinal genitourinary tracts) Platelets are not only involved in platelet plug formation but are also crucial for formation of fibrin (secondary hemostasis) Activated platelets express a negatively charged phospholipid phosphatidylserine (PS) on their surfaces which is a binding site for the assembly of coagulation factor complexes Assembly of these complexes on this surface markedly amplifies fibrin formation (called the propagation phase of secondary hemostasis) In addition activated platelets also activate neutrophils leading to NETosis or extrusion of nuclear material (Carestia et al 2016) which is strongly procoagulant and antifibrinolytic (Liaw et al 2015) ConstituentsPlatelets von Willebrand factor (vWf) integrins and extracellular matrix components in the Platelet capture and adhesion Upon endothelial injury platelets bind to exposed subendothelial matrix proteins such as collagen with the aid of adhesion molecules or receptors on their surfaces These receptors are transmembrane glycoproteins (GP) and are nonintegrin or integrin receptors Which receptors are involved in adhesion depends on the flow forces in the vessels At higher shear rates eg arterioles platelets need to be slowed before they can firmly adhere which is mediated by strands of vWf that unfurl f Platelet activation The adhesion of platelets to subendothelial matrix proteins activates the platelets (increasing intracellular calcium and inducing cell signaling) and causes a variety of changes in platelets Binding of the nonintegrin membrane protein GPVI optimizes collageninduced platelet activation after adhesion has occurred (Kuijpers et al 2004 Estevez and Du 2017) 1 Shape change Platelets change from their normal discoid shape to elongated cells with cytoplasmic extensions which increases the Platelet aggregation This is mediated primarily by fibrinogen which binds to the activated fibrinogen receptor (GPIIb/IIIa) on platelets This links platelets together forming the primary plug The platelet plug is sufficient to stop bleeding from most small blood vessels in response to every day trauma (eg eating) or venipuncture however in larger vessels or with more severe damage the primary platelet plug must be stabilized to cease the hemorrhage This is accomplished through secondary hemostasis or fibr There are physiologic pathologic and pharmacologic inhibitors of primary hemostasis 1 Physiologic Endothelial cells release prostacyclin (PGE12) and nitric oxide both of which inhibit platelet activation They also form a physical barrier preventing platelets from being exposed to thrombogenic subendothelial matrix proteins 2 Pathologic High concentrations of fibrin(ogen) degradation products can inhibit platelet aggregation (fragments D and E have a high affinity for platelet membranes and compete with fibrinogen for platelet receptors thus impairing aggregation) as can paraproteins (high concentrations of monoclonal immunoglobulins with multiple myeloma – the monoclonal protein coats platelets interfering with platelet aggregation adhesion and phospholipid exposure) 3 Pharmacologic These inhibit the following platelet activation events Note Drugs that inhibit platelet function can precipitate or worsen hemorrhage in an animal with a mild hemostatic disorder 31 A defect in any aspect of primary hemostasis can manifest as hemorrhage typically from mucosal surfaces (the sites where the primary platelet plug is important due to rapid fibrinolysis) Hyperactivity in primary hemostatic components is a cause of hypercoagulability and a risk factor for thrombosis 1 Defective primary hemostasis Platelet plug formation is inadequate with a defect in any primary hemostasis event including thrombocytopenia This usually manifests as hemorrhage from small blood vessels subjected to daily minor trauma ie those supplying mucuosa (eg epistaxis hematuria) Hemorrhage can be spontaneous with severe defects or induced by trauma or surgery with milder defects Since platelets plug small holes in vessels thrombocytopenia or abnormal platelet function (thrombopathia) can result in pinpoint mucosal or cutaneous hemorrhages (petechiae) Petechiae are not typical in vWD Bruises (ecchymoses) can also occur 2 Hyperactive primary hemostasisPlatelet h Two samples are required to evaluate primary hemostasis 1 EDTAanticoagulated blood Platelet count genetic testing (if needed) 2 Citrateanticoagulated plasma All other tests Please refer to the sample collectionpage for additional guidelines on how to collect samples appropriately to optimize hemostasis test results It is imperative that a platelet count is done in all animals presenting with clinical signs of excessive hemorrhage Platelet counts can be quantified using automated analyzers or can be semiquantified (estimated) from a wellprepared fresh blood smear Additional platelet testing requires fresh blood or preferably referral of the patient to a testing center that is capable of performing advanced hemostasis testing Few tests of primary hemostasis are available to general practitioners These include a platelet count a buccal mucosal bleeding time (BMBT) genetic testing for specific inherited disorders and measurement of vWf concentrations 1 Screening testsPlatelet count BMBT platelet function analyzer testing 2 Specific tests von Willebrand factor antigen (vWfAg) genetic testing for vWD and defined inherited thrombopathias (eg CalDAGGEF1 defect in Bassett Hounds and Eskimo Spitz GPIIb/IIIa deficiency or Glanzman’s thrombasthaenia in Otterhounds and Great Pyrene Defects arise in any aspect of the hemostatic pathway As indicated above these defects can result in deficient hemostasis (hypocoagulability) which can result in excessive hemorrhage or accelerated hemostasis (hypercoagulability) which can result in thrombosis Disorders can also be inherited or acquired Inherited conditions should be suspected in young animals presenting with episodes of recurrent hemorrhage or thrombosis Acquired disorders are more likely in older animals with underlying disease The most common inherited defect in primary hemostasis is von Willebrand Disease and thrombocytopeniais the most common acquired defect (there are multiple causes of thrombocytopenia).