Disorders of Haemostasis Flashcards
what is physiological haemostasis
- is the balance between CLOTTING MECHANISMS AND CLOT LYSIS
- the control of: internal and external bleeding
- the prevention of pathogical thrombosis
which factors maintain physiological haemostasis
- BLOOD VESSELS - vasoconstriction to reduce blood loss
- PLATELETS - initial haemostatic plug
- BLOOD COAGULATION - fibrin, permanent haemostatic plugs
- FIBRINOLYSIS - plasmin to remove fibrin thrombi
what is the role of platelets in clotting
- role is in the EARLY PHASE OF HAEMOSTASIS act via
1) ADHESION - platelets are attracted to exposed collagen
- activation: release of cytoplasmic granules
2) AGGREGATION: - accumulation/aggregation of LARGE NUMBERS of platelets to form haemostatic plug
describe blood coagulation and the roles of enzymes and ifactors in this process
- blood coagulation is req for events where platelets alone cannot stop blood loss
- PLASMA PRECURSORS in blood –> forms FIRBRIN –> which forms a PERMANENT HAEMOSTATIC PLUG
- activation of a series of clotting factors that are normally present in the INACTIVE FORM
- THROMBIN is the key enzyme
- some factors are SERINE PROTEASES
- many clotting factors are synthesised in the LIVER
- some (II, VII, IX, X) require VITAMIN K for their synthesis
what is the effect of a Vit K deficiency on blood clotting
- factors II, VII, IX and X req for blood clotting req VIT K
- O if there is a Vit K deficiency there may be lower levels of coagulating factors
- O more tendency to bleed
what are the 3 pathways in coagulation
1) intrinsic
2) extrinsic
both come to common pathway
what can intiate the intrinsic/extrinsic pathways
- damaged vessel (intrinsic)
- tissue damage (extrinsic)
do the intrinsic and extrinsic pathways act separately
no they act together
- there is feedback
- when factor VII is activated in the EXTRINSIC pathway, factor IX is stimulated from the INTRINSIC PATHWAY, thus stimulating it (+ve feedback)
why are factors VIII and IX important
cause haemophilia a and b
what is fibrinolysis
- once bleeding stops, this is the process to enzymatically break down the fibrin in blood clots (to prevent thrombus formation)
describe fibrinolysis
- PLASMIN breaks down fibrin –> fibrin dgradation products
- plasmin is formed form the conversion of PLASMINOGEN to plasmin using t-PA (tissue plasminogen activator) and XIIa and IIa
- t-PA is released when there is tissue damage
- XIIa and IIa are CLOTTING FACTORS that also have a role in converison of plasminogen to plasmin
which process is more predominant, clotting or fibrinolysis?
fibrinolysis under normal conditions (if there is no cell injury)
how can we diagnose and treat haemostatic disorders
we need clinical laboratory testing
- vast array of lab tests used to assess haemostasis
what is the role of routine and specialised tests of haemostasis
why do we use control plasma
- routine tests determine normal haemostasis
- specialised tests used to determine the type of abnormality if an abnormality has been found in routine testing
- control plasma: all tests must have control sample run at the same time as tests will VARY BETWEEN LABORATORIES so the difference between the control and patient may be more important than normal ranges
- this is an INTERNAL CONTROL
how are samples collected for testing
- a clean venous blood sample for coagulation
- blood should IMMEDIATELY be put into plastic tubes cont the appropriate anticoagulants
1) POTASSIUM EDTA: full blood count
2) SODIUM CITRATE: clotting studies - blood should be GENTLY MIXED
- blood should be tested ASAP (
why do samples need to have platelets removed
how can we achieve this
if the sample cont platelets, it will IMMEDIATELY activate clotting factors
- so we need PPP (platelet poor plasma)
- Accurate coagulation testing requires the plasma free of platelets (except platelet function tests)
- Immediately spin the sample (3000rpm, 10 min)
- Keep the sample at room temperature until PPP obtained to prevent platelet activation
- Test immediately or remove the plasma and store (at 4degreesC for a few hours or - 40degreesC for several wks)
where can pre-analytical and analytical variation affect coagulation results
- PRE ANALYTICAL:
- Poor sample collection
- Wrong anticoagulant / no anticoagulant
- Contamination
- Storage / transportation
- ANALYTICAL VARIATION:
- Incorrect temperature for analysis
- Out of date or poorly prepared reagents
- Out of date or poorly prepared control material
what are the routine tests of haemostatic function and what do they test
1) BLEEDING TIME: an index of PLATELET INTEGRITY
2) ACTIVATED PARTIAL THROMBOPLASTIN TIME (APTT): tests for INTRINSIC and COMMON (XII, XI, IX, VIII, X, V, II & I)
3) PROTHROMBIN TIME (PT) :
tests for EXTRINSIC and COMMON ((VII, X, V, II & I)
what are the specialised investigations/tests of haemostatic function and what do they test
1) 50:50 CORRECTION STUDIES (APTT):
- with normal plasma
- with normal deficient plasmas (to find out which is deficient)
2) FACTOR ASSAYS (level of deficiency of that factor)
3) INHIBITOR STUDIES (abnormal inhibitor to coagulation)
what are the major types of haemostatic disorders
what is involved
1) DISORDERS OF PRIMARY HAEMOSTASIS
- platelet abnormalities
- defects of small blood vessels
- SKIN AND MUCOUS MEMBRANE ESPECIALLY INVOLVED
2) DISORDERS OF BLOOD COAGULATION
- congenital clotting factor deficiency
- acquired disorders of coagulation
- typically: haemarthroses, muscl haematomas, bleeding after injury/surgery
abnormalities of blood platelets can cause bleeding how?
characterised by what
bleeding due to:
- thrombocytopenia (low platelet count)
- abnormal platelet function
- characterised by purpura (blood spots) and bleeding from mucous membranes
- symptoms are related to platelet count:
>80 x10^9/L - no clinical defect
< 50 x10^9/L- bleeding after trauma
< 20x10^9/L - spontaneous bleeding
what are the cuases of thrombocytopenia
- failure of production
- inc destruction
- sequestration
describe failure of production as a cause of thrombocytopenia
can be caused by:
- Megaloblastic anaemia
- Haematological malignancy
- Solid tumour infiltration
- Aplastic anaemia/bone marrow failure
describe increased destruction/use of platelets as a cause of thrombocytopenia
can be due to:
- Autoimmune (ITP Idiopathic thrombocytopenic purpura )
- Secondary immune (SLE, viruses, drugs)
- Alloimmune (neonatal & post-transfusion purpura)
- DIC (disseminated intravascular coagulation)
- Thrombotic thrombocytopenic purpura
describe sequestration as a cause of thrombocytopenia
- hypersplenism (spleen hides platelets when there is liver dysfunction)
describe idiopathic thrombocytopenic purpura (ITP) as a cause of thrombocytopenia
- Bleeding disorder due to immune destruction of platelets
- causes and pathogenesis:
Immune system produces platelet Ab –> Ab attach to platelets –> spleen destruction - ITP in children: usually acute but self-limiting; bone marrow examination not usual
- ITP in adults: less acute than in children; characteristically in women; associated with other autoimmune disorders (e.g. SLE); platelets Ab in 60-70% patients
what are the clinical features of ITP (idiopathic thrombocytopenic purpura)
what does laboratory investigation show
- Major haemorrhage rare, seen only with severe thrombocytopenia
- Easy bruising, purpura, epistaxis, menorrhagia
- Physical examination: normal except evidence of bleeding
laboratory investigation shows:
- Thrombocytopenia: the only blood count abnormality
- Anti-platelet auto-antibodies
how is ITP (idiopathic thrombocytopenic purpura) treated in children and adults
children:
- don’t usually req treatment
- but if necessary: High dose anti-inflammatory steroid. −i.v. immunoglobin (very serious bleeding, urgent surgery)
in adults:
- Platelets ≥30x10^9/L - no treatment
- First line: corticosteroids (iv IgG if rapid platelets rise desired)
- Second line: splenectomy (majority respond), if fails other treatments (high dose corticosteroids, immunosuppresion; recombinant thrombopoietin)
- Platelet transfusion (intracranial or other extreme haemorrhage)
what can disorders of blood coagulation cause
- Coagulation/fibrinolytic disorders may cause thrombosis or haemorrhage
- can be congenital or acquired
- majority are acquired
describe congenital coagulation disorder
- Uncommon and usually involve deficiency ofone factor only
- Deficiencies of all factors have been described
- Clinically most important:−Haemophilia A −Haemophilia B
- Von Willebrand’s disease
describe haemophilia A
- Haemophilia A (classic haemophilia)
- inherited as X-linked, recessive trait; 1 per 10,000 population
- occuring mainly in males
- deficiency of factor VIII (FVIII)
what are the clinical features of haemophilia A
Clinical severity depends on residual FVIII activitity
- < 1%, bleeding spontaneously
- 1-5%, bleeding after minor trauma
- > 5%, asymptomatic
- coagulation deficiency type bleeding
- spontaneous bleeding into muscle, joints;bleeding after dental surgery typical
- purpura not a feature
- AIDS is a majorcomplication in some patients due to treatment with FVIII concentrate
what are the laboratory features of haemophilia a
- Partial thromboplastin time prolonged
- FVIII ↓ decreased (<20%)
- Prothrombin time & bleeding time: normal
what is the treatment for haemophilia a
- Maintaining plasma FVIII activity at a level that permits normal physical activity without bleeding
describe haemophilia b
- Haemophilia B (Christmas disease) is uncommon (1 in 50,000)
- deficiency in factor IX
- X-linked recessive inheritance, greater prevalence in males
- Clinical picture identical to haemophilia a
what is Von Willebrand’s disease
- a mild to moderate bleeding disorder
- deficiency/abnormality of Von Willebran Factor (vWF, a glycoprotein; essential cofactor for platelet adhesion & also stabilising factor VIII)
causing:
- abnormal platelet adhesion- - low factor VIII clotting activity
caused by:
- Autosomal gene, numerous mutations identified
what is acquired coagulation disorder
Coagulation factor deficiency developed in some diseases or by drug therapies
- Vitamin K deficiency
- Liver disease
- Anticoagulant & fibrinolytic drugs
- DIC (Disseminated intravascular coagulation)
what is the effect of Vitamin K deficiency
- Some factors (II, VII, IX & X) are Vit K dependent
- Source of Vit K - green vegetables, gut microflora
- Lipid soluble, hence requires bile for absorption
- Therefore Vit K deficiency in obstructive jaundice & liver disease
- Haemorrhagic disease of the newborn – lack of gut flora
what is the effect of warfarin on vitamin K
A coumarin, potent Vit K antagonist
-Inhibiting complete synthesis of coagulation factors
what is the effect of liver disease
a number of defects in haemostasis:
- Vit K deficiency due to intra/extra hepatic cholestasis
- Reduced synthesis as a result ofsevere hepatocellular damage
- Thromocytopenia due to hypersplenism
- Functional abnormalities in platelets and fibrinogen
- DIC – in acute liver failure
