haemophilia Flashcards
product of coagulation cascade that allows secondary haemostasis
yields thrombin which converts fibrinogen to fibrin
- stabilises clot
fibrinolytic system
breaks down fibrinogen + fibrin
- activation of fibrinolytic system generates plasmin (in presence of thrombin) which is responsible for the lysis of fibrin clots
breakdown of fibrinogen + fibrin results in polypeptides results in polypeptides = fibrin degradation products = DDimer
how is fibrin converted to fibrin degradation products (DDimers)
by plasmin!
plasminogen –(tissue plasminogen activator)-> plasmin
disseminated intravascular coagulation (DIC)
excessive + inappropriate activation of haemostatic system (primary, secondary + fibrinolysis)
microvascular thrombus formation - end organ failure
clotting factor consumptom -> bruising purpura + generalised bleeding
pathophysio of DIC
process of coagulation + fibrinolysis are dysregulated -> result is widespreaf clotting with resultant bleeding
critical mediator of DIC = tissue factor (TF) - exposed to circulation after vascular damage
on activation, TF binds with coagulation factors that then triggers the extrinsic pathway (via factor VII) which subsequently triggers the intrinsic pathway (XIItoXItoIX)
causes of DIC
sepsis
trauma
obstetric emergencies - elevated LFTs, low platelets (HELLP)
malignancy - eats through tissue, slower process
hypovolaemic shock
investigation findings of DIC
low platelets
low fibrinogen
HIGH fibrinogen degradation products (DDimers)
high PT + APTT
schistocytes due to microangiopathic haemolytic anaemia
management of DIC
treat underlying cause
replacement therapy
- platelet transfusions
- plasma transfusions
- fibrongen replacement
prothrombin time, APTT, bleeding time + platelet count in warfarin administration
prothrombin time - prolonged
APTT - normal
bleeding time - normal
platelet count in - normal
prothrombin time, APTT, bleeding time + platelet count in aspirin administration
prothrombin time - normal
APTT - normal
bleeding time - PROLONGED
platelet count in - normal
prothrombin time, APTT, bleeding time + platelet count in heparin admin
prothrombin time - normal/maybe prolonged
APTT - prolonged
bleeding time - normal
platelet count - normal
prothrombin time, APTT, bleeding time + platelet count in DIC
prolonged - prothrombin time, APTT, bleeding time
LOW - platelet count
haemophilia
hereditary disorder in which abnormally prolonged bleeding recurs episodically
- no abnormaliry of primary haemostasis
x-linked recessive - 30% have NO fam history
types of haemophilia
haemophilia A (factor VIII def) - commonest
haemophilia B ( factor IX deficiency)
haemophilia features
recurrent haemarthroses (bleeds in joints)
- iron in these spots fuel neovascularisation - more blood vessels -> more prone to bleeds
recurrent soft tissue bleeds - bruising in toddlers
prolonged bleeding after denta extractions, surgery
investigation findings in haemophilia
prolonged APPT
normal bleeding time, thrombin time, prothrombin time
arterial thrombosis
high pressure system
atherosclerosis
platelet rich thrombus
Mx = aspirin + other anti-platelet drugs
- modify atherosclerosis risk factors
venous thrombosis
lower pressure system
virchows triad -> stasis, endothelial damage, hypercoagulability
platelets not activated
activates coagulation cascade - rich in fibrin clot
Mx = heparin/warfarin/new oral anticoags
extrinsic pathway
Tissue Factor (TF, factor III) activates VII to VIIa
VIIa activates X to Xa
common pathway
Xa + Va (prothrombinase complex) facilitates conversion of prothrombin (factor II) to thrombin
thrombin facilitates the conversion of fibrinogen (factor I) to fibrin (factor XIII, makes stable)
intrinsic pathway
sub endothelial collagen (SEC) exposed in vessel injury converts XII to XIIa which converts XI -> XIa which converts IX -> IXa
–> VIIIa + vWF activates conversion of X -> Xa
what inhibits the intrinsic pathway
heparin
how is the intrinsic pathway measured
APPT
what initially activates the intrinsic pathway
subendothelial collagen (SEC)
what inhibits the extrinsic pathway
warfarin
how is extrinisc pathway measured
prothrombin time
(extrinsic activated by tissue factor)
immune/idiopathic thrombocytopenic purpura (ITP)
an immune mediated reduction in platelet count
- antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IV
kids = usually have an acute thrombocytopenia that may follow infection or vaccination
adults = more chronic condition
ITP in kids
self limiting disease following viral infection/vaccination
bruising, petechial/purpuric rash
bleeding less common, typically present as epistaxis or gingival bleeding
no Mx - resolves in 80% within 6 months
- avoid activities involving trauma
ITP in adults
chronic relapsing disease - 85% spontaneously remit in 3-6months
commoner in older females
maybe detected incidentally following routine bloods
symptomatic - petechia, purpura, bleeding (epistaxis)
Ix - isolated thrombocytopenia, diagnosis of exclusion
management of ITP in adults
oral prednisolone
pooled normal human immunoglobin (IVIG) may also be used
- raises platelet count quicker than steroids, therefore may be used if active bleeding or an urgent invasive procedure required
Evans syndrome
ITP assoc with autoimmune haemolytic anaemia (AIHA)
thrombotic thrombocytopenic purpura (TTP)
abnormally cleaved von Willebrand factor (due to abnormal ADAMST13) leading to platelt aggregation, thrombus formation + systemic microangiopathu
rare, typically adult females
hereditary - congenital mutation of ADAMST13
autoimmune - AI inhibition of ADAMST13
pathophysio of TTP
abnormally large + sticky multimers of von Willebrands factor cause platelets to clump in vessels
in TTP there is a deficiency of ADAMST13 which breaks down (cleaves) large multimers of vWF
(overlaps with haemolytic uraemic syndrome)
features of thrombotic thrombocytopenic purpura(TTP)
fever
microangiopathic haemolytic anaemia (MAHA)
thrombocytopenic purpura
CNS involvement - headache, confusion, seizures
AKI/renal failure
TTP investigations
urine dip - haematuria + proteinuria (non-nephrotic range)
FBC - normocytic anaemia, thrombocytopenia, raised neutrophils
U&E - raised urea + creatinine
clotting normal
blood film - reticulocytosis (2nd to haemolysis) + schistocytes
LFT, LDH, DDimers raised + haptoglobins low - consistent with haemolysis
DIAGNOSIS = low ADAMST13 activity
management of TTP
plasma exchange started within 24hrs of presentation
caplacizumab(bivalent antibody)
