Coagulation - bleeding disorders Flashcards by Emily Southall

What can genetic defects effect -> bleeding disorders

plt - most common either thrombocytopenia or because of abnormal function

blood vessel wall

clotting factor deficiencies - haemophilias

excess clot breakdown - fibrinolysis

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which acquired defects can cause bleeding disorder

liver disease - clotting factor production
vit K deficiency
autoimmune disease -> plt destruction (thrombocytopenia)
trauma - damage to endothelium
anticoagulants/antiplatelets

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genetic defects -> thrombosis

clotting factor inhibitor deficiencies

decreased fibrinolysis

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disorders of haemostasis

vascular - scurvy, easy bruising

plt disorders - thrombocytopenia/abnormal function

coag disorder - factor def

mixed/consumption of coag factors and plts = disruption of coag system as whole -> DIC -> depletion of plt, clotting factors, fibrinogen -> life threatening condition, need to treat underlying cause

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features in hx that suggest type of disorder

Local VS generalised

haematoma/joint bleed - haemophilia/severe form of other disorder

skin/mucosal petechiae/purpura - plts or VWD

wound/surgical bleeding - factor 13 def, general global clotting problems

immediate - primary haemoststic plug - plts, endothelium, vWF

delayed - coagulation factor 8 9 11 (depend on age, FHx, ethnicity)

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why is bleeding with haemophilia delayed

no problem with primary plug - VWF, endothelium and plts

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clinical features of bleeding disorders

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what is this - and the type of bleeding disorder

petechiae
purpura

due to plt

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what is this - and the type of bleeding disorder

haemarthrosis

coagulation

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normal plt count

150-400

have to be much lower than 150 to get sx - so dont treat until less than 30 unless bleeding

Treat less than 30 - risk of intracerebral or mucosal haemorrhage -> fatal

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examining plts under microscope

confirm true thrombocytopenia - can get pseudothrombocytopenia where plts clump - usually due to EDTA

see rare things:
grey-plt syndrome
inclusion bodies in white cells - Döhle body-like leukocyte inclusions in May-Hegglin syndrome
rare hereditory microthrombocytopenic conditions - low plts, large plts, little bleeding tendency

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possible disorders of plts

thrombocytopenia
* decreased production
* decreased survival - autoimmune (ITP) - survival goes from 7-10days to a few hours
* increased utilisation - DIC

defective plt function
- acquired - drugs - aspirin, end-stage renal failure unless reg haemodialysis
- congenital - thrombasthenia - effect glycoproteins, granules, in plts - dx on platelet function analysis

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mode of action of anti-plt drugs

a lot of plts on dual antiplt agent - aspirin and clopidogrel - esp if MI and stent to stop stent blocking

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causes of thrombocytopenia

immune-mediated - related to immune dysregulation - plts recognosed as foreign and destroyed
* idiopathic
* drug-induced - quinine, rifampicin, vancomycin
* connective tissue disease - SLE, rheumatoid
* lymphoproliferative disease - CLL, leukaemias
* sarcoidosis

non-immune mediated
* DIC
* MAHA - blood cells haemolysed because of TTP

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Pathophysiology of auto immune idiopathic thrombocytopenia

autoAb tag the plts
as go through reticuloendothelium system
destroyed by macrophages
-> thrombocytopenia

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Differentiation of acute/chronic ITP

acute = children
chronic = adult

<20 is severe thrombocytopenia.
But children respond w/o Rx - dont get treated because risk of intracranial haemorrhage is rare

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Rx of ITP

depends on bleeding sx and level of plt count

IVIG compete with the autoAb - block receptor fro teh reticuloendothelial system and allow plts to last longer

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bleeding with ITP

Haematoma
petechiae - non-blanching
echymoses
sunconjunctival haemorrhage - superficial bleed

Ix of ITP

Blood film
* low plts
* macrocyte - B12/folate def - associated with thrombocytopenia
* acute leukaemia - myeloid blasts, Auer rods - cause thrombocytopenia

Inherited bleeding disorders - coagulation factor disorders

haemophilia A and B
vWB
other factor deficiencies (11, 10, 7, combined 8 and 5) - rare, present early in life, Rx with clotting factor

acquired bleeding disorders - coagulation factor disorders

liver disease
vit K deficiency/warfarin OD
DIC

Summarise haemophilia

congenital deficiency - factor 8 (A) or 9 (B)
bleeding = haematoma/joint
gene on X chr - carrier females, males suffer
long aPPT (intrinsic), normal PT

Rx- replace clotting factor - from plasma or recombinent factors

genetic inheritence of haemophilia

clinical manifestations of haemophilia

haemarthrosis (fixed joints) - most common
soft tissue haematomas (muscle) - muscle atrophy, shortened tendons
eccymoses
urinary tract bleeding
bleeding in CNS/Neck - life threatening
long bleeding after surgery/dentist

difference between haemophilia A and B

clinical features of vWD and inheritence

most common inherited bleeding disorder most have mild disease only - heavy period/nose bleed autosomal dominant mucocutaneous bleeding

Classification of vWD

type 1 - partial quantitative deficiency type 2 - quantitative deficiency - function reduced type 3 - total quantitative deficiency - very similar to haemophilia A because strong relationship between vWF and factor 8 - live together in circ, vWF protect factor 8 being destroyed in circ - if vWF not there = shorter life of 8

sources of vit K

green veg synthesised by intestinal flora

what factors need vit K

2 7 9 10 protein C protein S protein Z

Causes of vit K deficiency

malnutrition biliary obstruction malabsorption antibiotic therapy

Rx of vit k deficiency

**vit K - oral**, unless not going to absorb eg obstruction due to malignancy/stones - need **IM** but if impaired coag IM might = haematoma fresh frozen plasma

causes of DIC

**sepsis** trauma - head injury/fat embolism malignancy obs complications - amniotic fluid embolism, abruption placentae vascular disorder reaction to toxin - snake venom, drugs immunological disorders - severe allergic reaction, transplant rejection

how serious is DIC

life threatening could die in hours

dx of DIC

lab-clinical dx see lab changes - deranged aPTT, PTT, low fibrinogen, low plt, - factor 8 low - all consumed by **activation of coag and fibrinolysis **

paediatric case of DIC

meningococcal meningitis -> sepsis -> DIC Rx - clotting factor, plts, Rx meningitis - stop the drive

mechanism of DIC

deposition of fibrin -> kidney damage, brain damage, necrosis of extremities -> amputation depletion of plts and coag factors -> bleeding

Pathogenesis of DIC

release thromboplastic material into circulation -> 1. coagulation -> thrombin 2. fibrinolysis -> fibrin degredation product -> block circulation

DIC blood film

red cell fragments - red blood cells get sliced by the fibrin meshwork anaemia

Rx of DIC

treat underlying disorder anticoag with heparin plts FFP maybe recombinant activated protein C

how does liver disease -> coag problems

decreased synth of 2 7 9 10 11 and fibrinogen dietary vit K def 0 inadequate intake/malabsorption dysfibrinogemia - dysfunction of fibrinogen enhanced fibrinolysis - decreaed alpha-2-antiplasmin (inhibitor for plasmin activator) DIC thrombocytopenia due to hypersplenism

mx of haemostatic defects in liver disease

plasma and replace clotting factor when needed - as sx dictate

managing high INR levels from warfarin

danger of bleeding is related to INR - higher = more risk of bleed give Vit K or FFP or prothrombin complex concentrate containing 2 7 9 10 (because warfarin is vit K antagonist)

DOACs

Dont have an antidote