Haemostasis 2 Flashcards
what increases the incidence of bleeding disorders
- Consanguinity increases incidence 10-20 times – family history
define consanguinity
In clinical genetics, a consanguineous marriage is defined as a union between two individuals who are related as second cousins or closer
Name some rare bleeding disorders
- Factor XI,VII, V, X, II(prothrombin) deficiency
- Factor XIII and fibrinogen
- Combined V and VIII, vitamin K dependent factors deficiency
what area is a problem when bleeding
- Mucosal bleeding is more of an issue - therefore menorrhagia is a problem
list the severe platelet disorders
- Glanzmann’s – everything is normal in the assay
- Bernard-Soulier
what does the assay look like in glanzmanns
everything is normal in the assay
what does the assay look like in a deficiency of FVII
- platelet count
- PT
- APTT
- alteration
- platelet count = normal
- PT = abnormal
- APTT = normal
- alteration = coagulation
what does the assay look like in a deficiency of FVIII, FIX, FXI
- platelet count
- PT
- APTT
- alteration
- platelet count = normal
- PT = normal
- APTT = abnormal
- alteration = coagulation
what does the assay look like in a deficiency of Fibrinogen, FII, FV, FV+VIII, FX
- platelet count
- PT
- APTT
- alteration
- platelet count = normal
- PT= abnormal
- APTT = abnormal
- alteration = coagulation
what pathways does PT measure
extrinsic and common
What pathways does APTT measure
Intrinsic and common
for factor XI deficiency what population is predisposed
- Ashkenazi Jewish predisposition
- Genetics – dominant negative effects
what sites of surgery are important in a factor XI deficiency
- Mucosal and urogenital in particular
- Spinal and closed space
What is the treatment of factor XI deficiency
- Factor concentrate – plasma derived
- Avoid concurrent tranexamic acid – use one or the other (with factor 8 there used together all the time)
- Aim low normal levels (thrombotic potential)
- Long half life – alternate day dosing
- Consider thromboprophylaxis
describe factor VII deficiency
- Poor correlation levels and bleeding tendency – very low levels can be severe
- Very low levels may be very severe phenotype or coincidental pick up late in life
describe the treatment of factor VII deficiency
- Low dose recombinant fVIIa – 15-30ug/kg
what happens to factor VII deficiency in pregnancy
- VII levels may rise in pregnancy – mild/moderate may not need require replacement
- Possible compensation by other clotting factors rising in pregnancy
- Assess bleeding phenotype in non-pregnancy state
what happens in factor V deficiency
- Generally mild phenotype
- Don’t need much factor V for haemostasis (>15iu/dl)
- Some children have early, severe presentation – check VIII
How do you treat factor V deficiency
- No concentrate available
- Plasma – solvent detergent FFP – octaplas
describe a combined factor V and factor VIII deficiency
- Generally mild phenotype
- VIII and V genetics normal
- Abnormality of cellular transport (ERGIC)
What are the treatment options for factor V and VIII defficiency
VIII concentrate, DDAVP, plasma
what are the two types of fibrinogen deficiency
- Quantitative – afibrinogenemia(there is no fibrinogen)/hypofibrinogenemia (reduction in the amount)
- Qualitative – dysfibrinogenaemia (what you have doesn’t work properly)
- Coexist – hypodysfibrinogenaemia (both reduction and abnormal function)
what is the treatment for fibrinogen deficiency
Cryoprecipitate v fibrinogen concentrate
- Both plasmas derived
- Cryoprecipitate is not pathogen inactivated
- Fibrinogen concentrate – heat inactivated
What can fibrinogen deficiency care in pregnancy
- Recurrent miscarriage
- Abrupt and PPH
How much fibrinogen should you give during pregnancy
- Clearance increases during pregnancy
- Aim>1.0g/l during pregnancy
- Aim >2.0g/l for delivery
what happens in factor II deficiency
- Variable phenotype
- Think of other vitamin K dependent factors
what is the treatment for factor II deficiency
- Treatment = Prothrombin complex concentrate, plasma
- Symptomatic manoeuvres – mirena, COCP etc for menorrhagia
what is factor X deficiency and how do you treat it
- Some bleeding correlation with severity level
- May need to consider prophylaxis – prothrombin complex concentrate and plasma
what happens in factor XIII deficiency
- Numerical severity often reflects bleeding risk
- Bleeding symptoms from birth often diagnosed
- Prolonged umbilical stump bleeding
- Poor wound healing
How do you treat factor XIII deficiency
- Trials of recombinant XIII prophylaxis – market is cardiothoracic surgery (post cardiothoracic surgery bleeding can be a marker of this)
- Cryo or plasma
How do you treat vitamin K deficiency
- Prothrombin concentrate
- Plasma
- Check vitamin K given as neonate – haemorrhagic diseases of the newborn
- Vitamin K is given when they are born to remove the risk of haemorrhagic diseases of the newborn
what is glanzmanns disease
- Absent IIb/IIIa receptor on the platelet surface
- Platelets morphologically and numerically normal
what does glazmans look like in flow cytometry, platelet function test and platelet aggregometry
- PFA grossly abnormal (needs smaller amount of blood)
- Platelet aggregometry – absent response to all except ritocetin
- Flow cytometry – demonstrate absent IIb/IIIa
Platelet function test is abnormal
what happens in Bernard soulier
- Absent Ib/IX/V receptor on platelet surface – VWF receptor
- Platelets morphologically large and reduce in number – have thrombocytopenia
what does the
- PFA
- platelet aggregometry
- flow cytometry look like
- PFA abnormal
- Platelet aggregometry – absent response to ristocetin and others normal
- Flow cytometry – demonstrate absent Ib/IX/V
what is the treatment for both glanzmanns and Bernard souliers
- Platelet – ideal HLA matched/single donor
- Recombinant VIIa (90mcg/kg)
- Tranexamic acid
- COCP
- Bone marrow transplantation
what should you consider when dealing with a patient with blood factor deficiency
- Care around menarche
- Combined clinic with gynae
- Contraception
- Both for bleeding but also unwanted pregnancy
- Iron deficiency – bleeding and dietary
