Abnormalities of Haemostasis Flashcards
What is included in minor bleeding symptoms?
Easy bruising
Gum bleeding
Epistaxes (frequent nosebleeds)
Menorrhagia (women)
What counts as significant bleeding history?
- Epistaxis not stopped by 10mins of compression
- Cutaneous haemorrhage/bruise WITHOUT apparent trauma
- Prolonged bleeding from trivial wounds
- Menorrhagia requiring treatment or leads to anaemia
Why do people have abnormal haemostasis?
- LACK of a specific factor
o Failure of production - congential or acquired
o Increased consumption/clearance
- DEFECTIVE FUNCTION of a specific factor
o Genetic defect
o Acquired defect - drugs, synthetic defect, inhibition
Where can the problem lie with 1o haemostasis?
Formation of unstable platelet plug (2)
SO
Defects can lie in:
o platelets
o vWF
o collagen
How can a defect in platelets result in abnromal haemostasis?
- Low numbers - THROMBOCYTOPENIA
o Bone marrow failure e.g. leukaemia, B12 deficiency
o Accelerated clearance e.g. ITP, DIC
o Pooling and destruction in splenomegaly
- Impaired funcion
o Hereditary absence of glycoproteins (GpIIb/IIIa/Ib) /storage-granules (ATP etc.)
o Acquired from drugs e.g. aspirin, NSAIDs, Clopidogrel
How does auto-ITP work?
Auto-Immune Thrombocytopenic Purpura
- Anti-platelet Abs attack platelets
- These are engulfed by splenic macrophages
VERY common cause of thrombocytopenia
What can thrombocytopenia cause?
- Failure of platelet production by megakaryocytes
- Shortened half-life of platelets
- Increased pooling of platelets in an enlarged spleen (hypersplenism)
- also reduces its half-life in the spleen
What can a defect in vWF lead to?
Von Willebrand Disease
Explain the two forms Von Willebrand disease can form
- Hereditary DECREASE of quanity & function (most common form)
o Type 1 & 3 = DEFICIENCY of vWF
o Type 2 = ABNORMAL FUNCTION of vWF - Acquired due to an Ab (RARE)
What 2 functions does vWF have in haemostasis?
- Binding to collagen (to capture platelets)
2. Stabilising F8 (F8 may be low if vWF is very low)
Explain how defects in collagen/vessel wall can lead to abnormal haemostasis
o Inherited (rare)
- hereditary haemorrhagic telangisctasia
- Ehlers-Danlos syndrome (ONENOTE!)
- connective tissue disorders
o Acquired
- scruvy
- steroid therapy
- ageing (senile purpura)
- vasculitis
How can thrombocytopenia & severe vWF present clinically?
Thrombocytopenia = PETECHIAE
(very characteristic of LOW platelet count)
Severe vWF = haemophilia-like bleeding
What tests can you do to test disorders of 1o haemostasis?
- Platelet count / morphology
- Bleeding time (PFA100 in lab)
- Assays of vWF
- Clinical observation
Where can the problem lie with 2o haemostasis?
Stabilsiation of the plug with fibrin (3)
SO
with blood coagulation i.e. CROSSLINKED FIBRIN
Haemophilia Factor 8?
Failure of THROMBIN GENERATION
(due to F8 defects)
Thrombin provides much of the +VE feedback to convert fibrinogen –> fibrin
What does haemophilia Factor 8 mean for small and large vessel injury then?
Small vessel injury = 1o platelet plug is sufficient
Large vessel injury = 1o platelet plug will FALL apart
(remember - fibrin stabilises the platelet plug!)
Define haemophilia
Failure to generate fibrin to stabilise the platelet plug
What can decreased crosslinked fibrin be due to then?
- Deficiency of factor production
OR
- Increased consumption of factors
Explain how deficiency of factor production can lead to decreased crosslinked fibrin
Either hereditary or acquired
1. Hereditary o F8/9 - Haemophilia A/B - severe but compatible w. life - haemarthrosis (joint/muscle bleeding) o F2 (prothrombin) - lethal! o F11 - bleed after trauma - NOT spontaneous o F12 - NO excess bleeding at all
- Acquired - MORE COMMON
o Liver disease (decreased production)- most coagulation factors synthesised here
o Dilution e.g. transfusions
- RBC transfusions do NOT contain plasma unless major transfusion
o Anticoagulant drugs e.g. Warfarin
Explain how increased consumption of factors can lead to decreased crosslinked fibrin
ALWAYS ACQUIRED
o DIC - disseminated intravascular coagulation
- Generalised activation of coagulation via. TF
- Associated w. sepsis, major tissue damage, inflammation
- Consumers & depletes coagulation factors, platelets and fibrinogen (via. activation of fibrinolysis)
- Deposits of fibrin in vessels = organ failure
o Immune - auto-Abs
Typical bleeding patterns in 2o haemostasis coagulation disorders?
- Superficial cuts do NOT bleed - as platelets
- Bruising is common BUT nosebleeds are RARE
- Spontaneous bleeding is deep, into muscles & joints
- Bleeding after trauma may be delayed and is prolonged
- Bleeding frequently restarts after stopping
What should be avoided in patients w. haemophilia (or a 2o defect)?
Intramuscular injections!!
look at ONENOTE picture
Clinical distinction between bleeding due to platelet and coagulation defects?
Platelet/Vascular
o SUPERFICIAL bleeding into skin, mucosal membranes
o Bleeding IMMEDIATELY after injury
Coagulation
o Bleeding into DEEP tissues, muscles, joints
o DELAYED but SEVERE after injury
o Bleeding often PROLONGED
Tests for 2o haemostasis?
- Screening tests (‘clotting screen’)
o Prothrombin time (PT)- Extrinsic & common pathway defects (12,11,9,8,5,10,2)
o Activated partial thromboplastin time (APTT) - Intrinsic & common pathways defects (7,5,10,2)
o FBC (for platelets)
- Extrinsic & common pathway defects (12,11,9,8,5,10,2)
- Factor assays e.g. for F8
- Tests for inhibitors
