Bleeding Disrders Flashcards

Question

AUTO/ALLOIMMUNE COAGULATION DISORDERS

Answer 1

Caused by circulating antibodies to coagulation factors • Alloantibodies to factorVIII occur in5-10% of haemophiliacs Lupus anticoagulant • Interferes with lipoproteins and the phospholipid-dependant stages of coagulation • Anti-phospholipidsyndrome–LA orAPS inhibitor is detected in 10%of systemic lupus erythematosus(SLE)patients

Answer 2

Platelet count : 1)liver disease=low 2)DIC=LOW 3)massive transfusion=low 4)Circulating anticoagulant=normal Pt Liver disease/DIC/massive transfusion/circulating anticoagulant =prolonged Activated partial thromboplastin time Prolonged for everything

Answer 3

X chromosome-linked bleeding disorders • Deficiency of FVIII is haemophilia A • Deficiency of FIX is haemophilia B (Christmas disease) • Prolonged and excessive bleeding

Answer 4

• HaemophiliaAandBareX-linkedrecessive–predominantlyaffectsmales • GenesareclosetogetheronthelongarmoftheXchromosome. • Deletionsaccountfor5%ofcasesframeshift,missenseandinversionsarealsoseen. • ‘Flip’inversion-50%ofseverecases • Femalecarrierswillhave variable levels of FVIII of FIX due to random inactivation of theX chromosome

Answer 5

• FactorIXisakeyfactorofthe INTRINSIC pathway • WhydoesFIXdeficiencyresultina profound bleedingdisorder? FIX activation to FIXaby thrombin Amplification!

Answer 6

• Inheritedbleedingdisorderresultingfromlowfunctionallevelsofbloodcoagulation factor VIII • CausedbymutationsinthecoagulationfactorVIIIgene • Mostcommonofthesevereinheritedbleedingdisorders • (1caseper5,000male births) • Bleedingepisodesmaybemorefrequentinchildhoodandadolescencethanin adulthood. • Approximately10%ofcarrierfemalesareatriskforbleeding

Answer 7

• Family history - Usually diagnosed in the neonatal or prenatal period. • In sporadic cases (30%–40% of cases), the severe patients are diagnosed < 1 year old because of mucosal or soft tissue haemorrhages, usually after trauma • Haemophilia A is diagnosed in individuals with low factor VIII clotting activity in the presence of a normal von Willebrand factor (VWF) level • Molecular genetic testing of F8, the gene encoding factor VIII, identifies pathogenic variants in as many as 98% of individuals with haemophilia A

Answer 8

➢ General - Weakness and orthostasis ➢ Musculoskeletal(joints) ➢ Tingling, cracking, warmth, pain, ➢ Centralnervoussystem(CNS) ➢ Headache,stiff neck,vomiting,lethargy irritability, spinal cordsyndromes ➢ Gastrointestinal(GI) ➢ Haematemesis, abdominal pain ➢ Genitourinary ➢ Haematuria,post-circumcisionbleeding ➢ Excessivebleeding with routinedental procedures

Answer 9

Abnormal • Activated Partial Thromboplastin Time (APTT) - increased • Factor VIII/FIX clotting assay – Low Normal • VWF levels normal and normal function • Plateletcount • Prothrombintime(PT) • Platelet function analysis (PFA-100)

Answer 10

• Severe–concentratedfactorsusually prophylactically to prevent bleeds • Moderate–concentratedfactorswhenneeded • DDAVP(Desmopressin)whichinducesashort term rise in FVIII and von Willebrandfactor • Prothrombincomplexconcentrates(FIX) • Mild –DDAVPorProthrombinconcentrateswhen compromised ie surgical procedures

Answer 11

• Most common hereditary coagulation abnormality affecting ~1% of the population • QuantitativeorqualitativedefectinvonWillebrandfactor • Divided into three major categories 1. Type I – Partial quantitative vWF deficiency 2. Type II – Qualitative vWF deficiency 3. TypeIII -TotalvWFdeficiency • Affects individuals of all ethnic backgrounds, and the clinical symptoms can present at any age

Answer 12

• VWF is a large multimeric glycoprotein. • Synthesised by endothelial cells and in megakaryocytes • Endothelial cells are the main source of circulating VWF • Mature VWF is stored as Weibel-Palade bodies in endothelial cells and in the alpha granules of platelets • VWF is important for both PRIMARY and SECONDARY Haemostasis • Primary: Serves as a bridge between GPIb/IX receptors on activated platelets and subendothelial collagen exposed when the vessel is injured • Secondary: Complexes and stabilises FVIII in plasma

Answer 13

• Type 1: mild to moderate quantitative deficiency of VWF • Type 3: severe quantitative deficiency of VWF • Type 2: qualitative deficits in VWF. • Types 1, 2A, 2B, and 2M autosomal dominant trait • Type 3 and 2N is inherited as autosomal recessive

Answer 14

• Nosebleeds (epistaxis) and haematomas • Easy bruising - common but nonspecific • Prolonged bleeding - after minor trauma to skin or mucous membranes • Oralcavitybleeding • Excessive menstrual bleeding (menorrhagia) • Improvement of bleeding symptoms with use of oral contraceptives • Gastrointestinal bleeding (but rarely occurs) • Delayed bleeding - may occur up to several weeks after surgery • Exacerbation of bleeding symptoms - After ingestion of aspirin

Answer 15

Abnormal • Plateletfunctionanalysis(PFA)–prolonged • VWF levels low or abnormal function • Activated Partial Thromboplastin Time (APTT) – normal or increased • Factor VIII clotting assay – may be slightly reduced Normal • Factor IX assay • Plateletcount • Prothrombintime(PT)

Answer 16

• Quantitative – VWF:Ag assay • Determines the level VWF in the blood by measuring the vWF protein (antigen) • Measures the concentration of VWF, gives no indication as to function. • Typically by ELISA or immunoassays • Qualitative - VWF activity (Ristocetin Induced Platelet Aggregation) • Multimer analysis – differential diagnosis (distinguish between different types of VWD)

Answer 17

• Ristocetin–bindstoVWFandplateletGPIbtocause agglutination • Ristocetinusedasanantibioticuntilitwasrecognisedto causethrombocytopenia • RistocetinCofactor[vWF:RCo]assay measures the ability of a patient’s plasma to agglutinateplateletsinthepresenceof theantibiotic Ristocetin. • TherateofRistocetininducedagglutinationis relatedtothe concentrationandfunctional activity of the plasma von Willebrand factor.

Answer 18

Absence of multimers depending on the type of disease

Answer 19

• TwomaintreatmentoptionsforpatientswithvonWillebranddisease(vWD) • Desmopressin (DDAVP) • von Willebrand factor/factor VIII (vWF/FVIII)concentrates • DDAVPcausesthereleaseofVWFfromWeibelPaladebodies • PlatelettransfusionsmaybehelpfulinsomepatientswithvWD(eg,type3) • CryoprecipitateandfreshfrozenplasmacontainfunctionalvonWillebrandfactor(vWF) but should be avoided if at all possible because of the potential transmission of viral disease.