11 & 12. Disorders of Haemostasis Flashcards
(43 cards)
Defective haemostasis with abnormal bleeding may be caused by:
- abnormalities of vessel wall (vascular system)
- thrombocytopenia (cytopenia is reduction in number of cells and thrombocytopenia is lower number of platelets)
- disordered platelet function (thrombocytopathy)
- defective blood coagulation
vascular bleeding disorders
minimal blood loss, may be unknown to patients, bleeding and haemostatic tests appear normal
Characteristics
Easy bruising
Spontaneous bleeding from small vessels
Pathology
Abnormality in blood vessels
Bleeding and other haemostasis tests usually normal
Hereditary Haemorrhagic Telangiectasia
uncommon inherited vascular disorder
autosomal dominant
defects in at least three genes but only 1 gene is the cause in any one family
abnormally formed blood vessels results in thin walled capillaries
symptoms of Hereditary Haemorrhagic Telangiectasia
telangiectases - dilated microvascular swellings, easy to rupture and even smaller than purpura
see them on nose tongue and lips
nosebleeds and gastrointestinal blood loss
chronic iron deficiency frequent
treatment of Hereditary Haemorrhagic Telangiectasia
dependent on severity
embolization - guide the emboli to area where its needed, introducing an artificial clot
laser treatment - targeting areas which may be swollen
transexamic acid, antifibrinolytic agent, prevents plasminogen being converted to plasmin, plasmin normally acts upon fibrin to break fibrin clot down . so we miantaian clots, blood loss prevented
iron supplements
Hereditary Haemorrhagic Telangiectasia conc
Degenerate changes in blood vessel vasculature as the individual ages
Natural blood vessel atrophy as we age, elastin changes, composition of blood vessels more pore to changes that allow blood loss to occur
90-95%: at least a few telangiectasia on the skin of the face and/or hands by middle age
90-95%: nosebleeds by adulthood
Infrequent/minor to daily/severe.
20-25%: bleeding in the stomach or intestines, but rarely before 50 y.old.
Hereditary Haemorrhagic Telangiectasia cont
Degenerate changes in blood vessel vasculature as the individual ages
Natural blood vessel atrophy as we age, elastin changes, composition of blood vessels more pore to changes that allow blood loss to occur
90-95%: at least a few telangiectasia on the skin of the face and/or hands by middle age
90-95%: nosebleeds by adulthood
Infrequent/minor to daily/severe.
20-25%: bleeding in the stomach or intestines, but rarely before 50 y.old.
acquired vascular defects
Wide variety of causes: incl infections, drug reactions, trauma, old age and steroid use.
eg Vascular purpura can be categorized as such:
-Purpura simplex
common benign disorder, women of child bearing age.
-Senile purpura
old age, due to the loss of skin elasticity and atrophy of vascular collagen. Mainly on the forearms and hands.
-Infection associated purpura
Bacterial and viral infections, e.g. measles can cause purpura from vascular damage by the organism.
thrombocytopenia
deficiency in platelet numbers
defined as a low platelet count with values less than 150 x 109/L
3 main causes of thrombocytopenias:
1Failure of platelet production (in bone marrow)
2Increased destruction of platelets
3Sequestration (abnormal distribution) of platelets, is related to splenomegaly, enlarged spleen. more cells destroyed leading to overproduction of cells, more cells end up getting stuck going through the spleen and can lead to premature destruction, but it means that more of circulating platelets are in the spleen than circulating round the body so end up appearing as having thrombocytopenia
- failure of platelet production
Most common cause of thrombocytopenia
Usually part of bone marrow failure.
- aplastic anaemia (reduction in blood cells) or leukaemia (overproduction of wbc).
- Drug/viral induced toxicity
Diagnosis
clinical history, peripheral blood count, blood film and bone marrow examination
cure is bone marrow transplant
- increased destruction of platelets
Primary cause: autoantibodies attaching to the platelet surface and marking them for premature destruction
Autoimmune (idiopathic) thrombocytopenia purpura (ITP)-
Two disease categories:
chronic ITP and
acute ITP.
chronic itp
General features
Relatively common
Young women 15-50 y.old
Asymptomatic or insidious(gradual increase) onset of bleeding
Autoantibodies in their plasma and on their platelets.
Platelets sensitised with autoantibodies (mostly IgG): destroyed by macrophages in spleen and liver.
Antibodies : glycoprotein IIb/IIIa or Ib. glycoproteins normally attach the platelet to damaged blood vessel surface, attacking them means destruction of platelets
Platelet lifespan considerably reduced: as little as a few hours! Cannot form platelet plug
acute ITP
General features
-Children under 10
-Majority, onset is abrupt following vaccination or a viral episode (chicken pox, measles).
-Post viral cases:
likely IgG antibody attaches to viral antigen absorbed onto the platelet surface
dramatic fall in platelet count to less than 20 x 109/L.
-Spontaneous remissions usual
-Minority of cases develop chronic ITP
- sequestration of platelets
Normal situation: spleen contains approx 30% of all platelets.
Splenomegaly:
up to 90% of platelets may be sequestered in the spleen
leading to thrombocytopenia
more than normal platelet number in spleen so platelets not in circulation, not available to form platelet plug leading to reduction in numbers of platelets
Thrombocytopathy
Disorders of Platelet Function
Considered when clinical signs and symptoms of thrombocytopenia but in the presence of a normal platelet count.
Inherited and Acquired disorders
Inherited disorders: rare but capable of producing defects at each of the different phases of the platelet reaction (activation, adhesion, secretion, aggregations).
Acquired disorders: much more common.
Acquired Disorders of Platelet Function
1) Antiplatelet drugs (Aspirin)
2. Haematological malignancy
- antiplatelet drugs (aspirin)
1) Antiplatelet drugs (Aspirin)
Irreversibly inactivates the enzyme cyclooxygenase (COX),
Prevents production of thromboxane A2 from arachidonic acid so prevents vasoconstriction
Result: inhibition of platelet aggregation
Significantly extends bleeding time
haemorrhage in patients with thrombocytopenia, especially if you don’t know you have the condition and self administer.
- haematological malignancy
E.g.
acute myeloid leukaemia,
any myeloproliferative disorders and myeloma.
diagnosis of platelet disorders
Initial blood count and blood film examination, tells u contents of circulation not bone marrow
Bone marrow biopsy:
-thrombocytopenic patients
-ascertain failure of platelet production
Blood count: within normal limits
other tests performed to detect abnormal platelet function
Prolonged bleeding time detected
defect usually acquired and should be evident on clinical investigation
Patients with hereditary defects require further testing to define the specific abnormality.
Defective Coagulation
Inherited and acquired defects
Inherited coagulation disorders: one of three disorders,
Haemophilia A
Haemophilia B
von Willebrand’s disease
haemophilia A
Most common hereditary clotting factor deficiency
Deficiency in factor VIII (cofactor for factor IX): Mutations lead to under production of factor VIII and clinical syndrome of haemophilia.
Prevalence 30-100 per million of population
X linked recessive disorder
All males with defective gene having haemophilia
All sons of haemophiliac men are normal
All daughters are carriers
Can be spontaneous mutation with no family history
clinical features of haemophilia A
Severity of bleeding is related to the factor VIII level
Clinical features of severe haemophilia
Bleeding into joints and less frequently muscles
Knees, elbows and ankles most commonly affected - haemarthosis
Majority of bleeds that require treatment.
Presenting symptoms: pain in affected areas.
Intracranial bleeding: main cause of death from the disease.
High death rate: HIV-contaminating factor VIII observed in the USA and Europe in the last two decades.
diagnosis
Prolonged activated partial thromboplastin time (APTT).
Confirmed by a factor VIII clotting assay.
Carrier detection and antenatal diagnosis uses DNA technology.
Chorionic biopsies at 8-10 weeks of gestation provide DNA for analysis.
symptoms of haemophilia A
Concentration of coagulation factor (% of normal) and Bleeding episodes
- 50-100 NONE
- 25-50 bleeding tendency after severe trauma
- 5-25 (mild): Severe bleeding episodes after surgery, slight bleeding episodes after minor trauma
- 1-5 moderate: Severe bleeding episodes even after slight trauma
- <1 (severe): Severe, frequent spontaneous bleeding episodes predominantly in the joints or muscles
