W7: Bleeding Disorders Flashcards
diff btwn primary + secondary haemostatic disorder
primary hemostasis = formation of primary platelet plug
secondary hemostasis = coagulation cascade/formation of blood clot
examples of PHD + SHD
PHD = thrombocytopenia
VWD
SHD = haemophilia
PHD vs SHD: bleeding
p - immediate
s - delayed
PHD vs SHD: petechiae
p - yes
s - no
PHD vs SHD: epistaxis
p - common
s - uncommon
PHD vs SHD: menorrhagia
p - common
s - uncommon
PHD vs SHD: Haemarthroses
p - no
s - yes
PHD vs SHD: intramuscular haematomas
p - uncommon
s - common
PHD vs SHD: gender
p - equal
s - >80% male
Bleeding defects may result from
leaky vessels
low platelet number (thrombocytopenia)
low platelet function
low coagulation
Thrombocytopenia - Causes
Failure of marrow production
Drug-induced
DIC
Sequestration - pooling of platelets in Splenomegaly
Massive blood transfusion-> dilution
define ITP - Idiopathic thrombocytopenic purpura (immune destruction)
Sudden onset of immunological destruction of platelets and thus thrombocytopenia.
ITP acute vs chronic
A
Sudden onset in children, often after illness.
90% spontaneous remission after few weeks
C
Gradual onset in adults (3F:1M) (no previous viral infection)
Autoantibodies (antibodies against self)
Platelets destroyed in spleen + liver (within a few hours).
usually lifelong condition
ITP diagnosis (A +C)
Low platelet no.
Large platelets
[Hb] + WBC typically normal
Tests for autoantibodies
ITP treatment (A vs C)
A - observation
C - Corticosteroids (supress immune sys)
Splenectomy
Immunosuppressive drugs
Platelet transfusions (short term benefit)
Stem cell transplantation
define TTP - Thrombotic thrombocytopenic purpura
Formation of vWF multimers -> platelet aggregation (thrombosis) -> thrombocytopenia
2 types of TTP + diff
acquired - Ab blocks protease that breaks down vWF multimers
inherited - protease absent/ defective
TTP diagnosis
thrombocytopenia
schistocytosis, (fragmented RBCs)
incr serum LDH
Coagulation NORMAL unlike in DIC.
TTP treatment
Plasma exchange
to remove vWF multimers + Ab + provide protease
what’s DIC
disseminated intravascular coagulation
Thrombosis + bleeding at the same time (in diff parts of body)
DIC usually happens when what other conditions also occurring
Infections - sepsis
Malignancy
Wide spread tissue damage (surgery / trauma / burns)
Anaphylaxis
DIC treatment depends on whether patient bleeding (treatment x) or thrombotic (treatment y)
fresh frozen plasma
heparin
steps of platelet plug formation
adhesion
activation
aggregation
disorders of platelet function
inherited vs acquired
Inherited
Platelet adhesion defects
Activation defects
Secretion defects
Aggregation defects
Acquired
Aspirin and other drugs
Chronic renal failure
Cardiopulmonary bypass
Haematological diseases
what can vWF in plasma protein bind to on surface of platelets (2) + effect
collagen
GPIb complex
initial interaction not v strong so only slows platelet down
what’s most common inherited bleeding disorder
VWD
3 types of VWD + what does it depend on
Type 1: Quantitative partial deficiency
Type 2: Functional abnormality
Type 3: Complete deficiency
depends on autosomal recessive or dominant mutation
where is vWF prod (2) + roles (2)
endothelial cells + megakaryocytes
roles
platelet adhesion
carries FVIII prolonging its half life
vWF gene is on chromosome
12
VWD diagnosis
Usually normal platelet number + morphology
bleeding prolonged
aPTT prolonged
PT normal, TT normal
vWF levels often low
FVIII levels often low
VWD treatment
no treatment req
Education - drug avoidance (aspirin), contact sport avoidance
Genetic counselling
Desmopressin - induces release of vWF from endothelium
Tranexamic acid (antifibrinolytic)
what’s Bernard-Soulier Syndrome
inherited: platelet adhesion defect
GPIb complex
2 examples of inherited: activation defects
GPVI deficiency
cyclooxygenase deficiency
examples of inherited: secretion defects
Grey platelet syndrome
Platelets lack alpha granules ( so look grey)
Wiskott-Aldrich Syndrome
platelets (+ other cells) lack dense granules (+ are smaller) + thrombocytopenia
Example of inherited: Aggregation Defects
Glanzmann’s thrombasthenia
integrin aIIbB3 defect
Inability of platelets to bind fibrinogen + form platelet plug
Glanzmann’s thrombasthenia symptoms
Easy bruising
menorrhagia
Glanzmann’s thrombasthenia diagnosis
normal platelet no. + morphology
prolonged bleeding
Glanzmann’s thrombasthenia treatment
Education
Local haemostatic agents (“quick clotters”)
Platelet transfusions
Genetic counselling
Acquired Platelet Disorders: Aspirin + other drugs
Anti-platelet drug
Inhibits cyclooxygenase-1
decr in prod of thromboxane A2 (in platelets)
decr prod of PGI2 (in endothelial cells)
Acquired Platelet Disorders: Aspirin + other drugs treatment
platelet transfusion
desmopressin (induces release of vWF from endothelial cells)
Acquired Platelet Disorders: Chronic Renal Failure
Renal failure causes incr bleeding time due to either
Uraemia (high nitrogen in blood leading to multiple platelet defects)
Anaemia ( decr Epo synthesis by kidneys)
Affects platelet – vessel wall interactions
Acquired Platelet Disorders: Chronic Renal Failure treatment
RBC packs (bulk blood, pushing platelets to the vessel walls)
Platelet transfusions (limited effect as then in uraemic plasma)
Acquired Platelet Disorders: Cardiopulmonary bypass
Platelet activation and degranulation occurs in the extracorporeal circuit (out of the body).
Acquired Platelet Disorders: Cardiopulmonary bypass treatment
Platelet transfusion
Haematologial diseases:
Several blood diseases impair platelet function
Most of the leukaemias (bone marrow activity affected).
Myeloma (plasma B-cells ie bone marrow affected).
Reduced coagulation tends to arise from
A deficiency in a coagulation factor
Inherited incl. fibrinogen
Acquired
Inherited: Coagulation factor deficiencies
Haemophilia A
Deficiency in FVIII.
X-linked recessive disorder.
Mostly inherited, though 30% due to sporadic mutations.
Severity varies from mild to severe.
Inherited: Coagulation factor deficiencies
VWD
vWF carries FVIII
Most common inherited bleeding disorder
1:100 (asympt)
1:10 000 (sympt).
Autosomal dominant/recessive.
Inherited: Coagulation factor deficiencies
Haemophilia B
Deficiency in FIX.
X-linked recessive disorder.
Severity variable
other factor deficiencies - autosomal recessive
FXI
FVII
FV
FXIII
Abnormalities of fibrinogen
Quantitative deficiencies
Apofibrinogenaemia - Autosomal recessive. Severe symptoms.
Hypofibrinogenaemia - Less defined. Milder symptoms.
Qualitative deficiencies
Dysfibrinogenaemia- Autosomal dominant. haemorrhagic effect (50%)
thrombotic effect (10%)
Acquired: Coagulation factor deficiencies (3)
Liver Disease
site of synthesis of several clotting factors (+ thrombopoietin)
Liver function tests include: Albumin, Bilirubin, Prothrombin Time
Vitamin K deficiency
The reduced form of Vitamin K is needed for post-translational modification of several clotting factors (when synthesised).
Warfarin use
Warfarin inhibits the enzyme that cycles Vitamin K (vitamin K epoxide reductase
Acquired: Coagulation factor deficiencies
Acquired haemophilia
diagnosis +treatment
Generally neutralising autoantibody against FVIII
Diagnosed with inhibitor assays
Treatment:
Human FVIII not effective
Recombinant porcine FVIII better
Immunosuppressive therapy
