S5) Haemostasis Flashcards
What are the principles of haemostasis?
- Prevent bleeding
- Prevent unnecessary coagulation (allow blood to flow)
- Make clot
- Control clotting
- Break it down
What are the essentials for haemostasis?
- Pump: heart, venous valves, calf pump
- Blood vessels are important
- Platelets
- Coagulation factors
- Anticoagulant factors
What are platelets?
Platelets are components of blood produced by megakaryocytes in the bone marrow and bud from cytoplasm
In three steps, outline platelet adhesion
⇒ Damage to the vessel wall
⇒ Exposure of underlying tissues
⇒ Platelets adhere to collagen via vWF/receptor
In 3 steps, outline platelet activation
⇒ Platelets secrete ADP, thromboxane, etc to become activated and activate other platelets
⇒ Involved in activation of the clotting cascade
⇒ Provide some coagulation factors by secretion from internal stores
What does platelet aggregation involve?
Platelet aggregation involves the cross linking of platelets to form a platelet plug
Identify 6 mediating factors in haemostasis
- Von willebrand factor
- Fibrinogen
- Collagen
- ADP
- Thromboxane
- Thrombin
What is the clotting cascade?
- The clotting cascade is a controlled amplification system involving the activation of precursor proteins to generate thrombin (IIa)
- Thrombin converts soluble fibrinogen into insoluble fibrin
- Fibrin enmeshes the initial platelet plug to make stable clot
Describe the control of the clotting cascade
- Natural anticoagulants inhibit activation
- Clot destroying proteins are activated by the clotting cascade
Identify some coagulation factors
- Fibrinogen
- Prothrombin
- Factor V, VII - XIII
- Tissue factor
Identify some natural anticoagulants
- Protein C
- Protein S
- Antithrombin
- Tissue factor pathway inhibitor
Describe the process of initiation in the clotting cascade?
Describe the process of amplification in the clotting cascade?
What is the role of Von Willebrand Factor?
VWF carries factor VIII and mediates platelet adhesion to the endothelium
Describe changes in the vessel wall during blood clotting
- Vasoconstriction
- Production of vWF (platelet adhesion, carrier of Factor 8)
- Exposure of collagen and tissue factor initiates activation of clotting factors
What is fibrinolysis?
Fibrinolysis is a process which prevents blood clots from growing and becoming problematic by breaking down fibrin clot, a product of coagulation
What is the clinical relevance of understanding haemostasis?
- Bleeding disorders
- Arterial thrombotic disorders
- Venous thrombotic disorders
- Abnormal blood test results
- Drug therapy for pro- or anti-thrombotic purposes
What are bleeding disorders?
Bleeding disorders are inherited/acquired conditions arising due to abnormality in the vessel wall, platelets or coagulation factors
Identify two congenital coagulation factor disorders
- Haemophilia A
- Haemophilia B
In coagulation factor disorders, clinical severity correlates with extent of deficiency.
Identify 5 clinical presentations of these disorders
- Muscle haematomas
- Recurrent haemarthroses
- Joint pain and deformity
- Prolonged bleeding (after dental extraction, operation, trauma)
- Intracerebral haemorrhage
What is Haemophilia A?
- Haemophilia A is an X-linked recessive disorder due to a congenital lack of factor VIII
- It can be mild/moderate/severe depending on amount of factor VIII present and is treated with recombinant factor VIII or DDAVP
What is Haemophilia B?
Haemophilia B is an X-linked recessive disorder due to the congenital reduction in factor IX
Identify two acquired coagulation factor disorders
- Liver disease
- Vitamin K deficiency
What is Von Willebrand’s Disease?
- Von Willebrand’s disease is a relatively common autosomal dominant disease often due to a reduction in vWF production
- There is abnormal platelet adhesion to the blood vessel wall as well as reduced FVIII amount/activiy
How does Von Willebrand’s Disease present clinically?
- Skin and mucous membrane bleeding: epistaxis, gum bleeding, bruising
- Prolonged post-traumatic bleeding: heavy periods, post surgery, post dental extraction
How do blood vessel wall abnormalities present?
- Easy bruising
- Spontaneous bleeding from small vessels (skin/mucous membranes)
Identify some congenital conditions causing problems with vessels
- Hereditary Haemorrhagic Telangiectasia (HHT)
- Ehlers Danlos Syndrome
Identify some acquired conditions causing problems with vessels
- Senile purpura
- Steroids
- Infection e.g. measles, meningococcal infection
- Scurvy
What are the two different types of platelet disorders?
- Qualitative
- Quantitative (thrombocytopenia)
Describe the different causes for thrombocytopenia
Describe the causes and treatment for the immune destruction of platelets
- Immune thrombocytopenic purpura is most common cause
- Can be secondary to autoimmune disease e.g lupus, lymphoma
- Treated with immunosuppression (corticosteroids or IVIg first line) as platelet transfusions do not work
Identify two circumstances wherein the non-immune destruction of platelets occurs
- Microangiopathic haemolytic states e.g. DIC
- Cardiopulmonary bypass surgery
Identify 4 causes of the reduced production of platelet cells
- B12 / folate deficiency
- Infiltration of the bone marrow by cancer cells/fibrosis
- Drugs (chemotherapy, some antibiotics)
- Viruses (HIV, infective hepatitis, EBV, CMV)
What are the consequences of severe thrombocytopenia?
- Easy bruising
- Petechiae, purpura
- Mucosal bleeding
- Severe bleeding after trauma
- Intracranial haemorrhage
What is Disemminated Intravascular Coagulopathy?
- DIC is a type of microangiopathic haemolytic anaemia due to the pathological activation of coagulation
- Numerous microthrombi are formed in the circulation which leads to consumption of clotting factors and platelets and a haemolytic anaemia
How does DIC present?
Symptoms are due to tissue hypoxia and infarction or haemorrhage:
- Respiratory compromise
- Convulsions and neurological symptoms
- Renal & hepatic failure
- Shock and cardiac failure
- Gangrene of the skin
Identify six triggers of DIC
- Malignancy
- Massive tissue injury e.g. burns
- Infections (Gneg sepsis)
- Massive haemorrhage and transfusion
- ABO transfusion reaction
- Obstetric causes (placental abruption, pre-eclampsia, amniotic fluid embolism)
Which clotting tests are affected in DIC?
- Raised PT/INR
- Raised APTT
- Low fibrinogen
- Raised D dimers
Why does DIC present with a low fibrinogen count and a raised D-Dimer count?
Fibrinogen is consumed in microthrombi formation, which is broken down by fibrinolysis leading to the release of fibrin degradation products e.g. D Dimers
What is PT and what are its uses?
- Prothrombin time (PT) is a blood test that measures how long it takes blood to clot
- It can be used to check for bleeding problems / to check if medication for bleeding problems is working
What is INR and what are its uses?
- The INR is a calculated ratio: (patient’s PT / mean PT)
- The INR (rather than PT ratio) is used for monitoring patients on warfarin
Provide some explanations for a patient presenting with an isolated prolonged PT
- Warfarin use for liver disease (APTT often also prolonged in severe liver disease)
- Vitamin K deficiency
- Paracetamol overdose
What are the indications for warfarin?
Treatment and prophylaxis for thrombosis, including:
- Thrombotic event e.g. PE/DVT
- Arrhythmias e.g. AF
- Cardiac valve replacement
What is warfarin’s main mechanism of action?
Warfarin inhibits synthesis of vitamin K dependent factors (II, VII, IX and X)
What is the likely explanation for a raised INR in a patient on antibiotics and warfarin (to treat a recent thrombotic event)?
Antibiotics (commonly trimethoprim, metronidazole, fluconazole, ciprofloxacin, levofloxacin, azithromycin, and clarithromycin) interfere with the metabolism of warfarin
A 68 year old man presents with severe septicaemia, bleeding from the arterial line puncture site and has haematuria and rectal bleeding.
Provide an explanation for the following abnormalities in his blood results:
Haemoglobin: 115 g/L (130-180)
MCV: 90 fl (80-99)
WCC: 20.8 x 109/l (4-11)
Neutrophils: 18.0 x 109/l (1.5-7.5)
Lymphocytes: 2.4 x 109/l (1-4)
Platelets: 15 x 109/l (140-400)
INR: 2.5
PT: 27 secs (12-15)
APTT: 70 secs (25-35)
Fibrinogen: 0.5 g/L (2.0-4.0)
D Dimers: 5mcg/ml (0-0.5)
- Normocytic anaemia – likely combination of microangiopathic haemolytic anaemia and bleeding
- Neutrophilia – bacterial infection
- Thrombocytopenia – likely due to microthrombi formation in the setting of DIC
- Combined prolongation of APTT and PT – global reduction in clotting factors
- Reduced fibrinogen – DIC
