Platelets + Disorders Flashcards
How are platelets formed
Formed by fragmentation of megakaryocytic cytoplasm in bone marrow
Advantage of platelets having a disc shape
Allows them to flow close to the endothelium
Lifespan of platelets
7-10 days
How are platelets broken down
Phagocytksed by splenic macrophages in red pulp
Where is thrombopoietin produced
Liver
How does liver damage effect platelets
Reduced thrombopoietin = decreased platelets
Compensatory mechanism for decreased TPO
More TPO able to bind to MK = increased platelet production
What precursor molecule is Thromboxane A2 made from
Arachidonic acid via COX-1
Role of Thromboxane A2
Induces platelet aggregation + vasoconstriction
What molecule activates P2Y12
ADP
Role of P2Y12
Amplifies activation of platelets + helps activate glycoprotein IIb/IIIa
Role of IIb/IIIa
Receptor for fibrinogen and vWF
What is vWF
clotting factor needed for platelets to adhere to damaged blood vessels
Role of IIb/IIIa
Aids platelet adherence and aggregation
What is vWF disease
reduced vWF activity = platelets are unable to bind to damaged blood vessels resulting in platelet dysfunction + muco-cutaneous bleeding
What is thrombocytopenia
Deficiency of platelets in th blood
What is congenital thrombocytopenia
- Malfunctioning megakaryocytes in bone marrow
What causes thrombocytopenia
- Infiltration of bone marrow (leukaemia, metastatic malignancy, lymphoma, myeloma, myelofibrosis)
- Reduced platelet production by bone marrow
What can result in reduced platelet production by bone marrow = thrombcytopenia
- Low B12/folate
- Reduced TPO
- Medication
- Toxins
- Infections
- Aplastic anaemia
What medication causes thrombocytopenia
- Methotrexate
2. Chemotherapy
4 ways increased DESTRUCTION of platelets = thrombocytopenia
- Autoimmune (ITP)
- Hypersplenism (portal hypertension + splenomegaly)
Drug-related immune destruction (heparin induced thrombocytopenia)
What disorders cause consumption of platelets
- DIC
2. TTP
How is ITP caused
Immune destruction by platelets
Antibody-coated platelets are removed following binding to Fc receptors on macrophages
IgG antibodies form to platelets and megakaryocytes
Where is primary ITP more common
CHildren
What age group does ITP mainly cause
2-6 years
Onset of ITP
Acute with much-cutaneous bleeding + history or recent viral infection (inc. chickenpox or measles)
Self-limiting Purport (red spots on skin due to bleeding underneath)
Is life-threatening haemorrhage common in ITP
No
When does Secondary ITP occur (chronic)
In adults
Gender does 2ndary ITP occur
Women
What autoimmune conditions is Secondary ITP associated with
- SLE
- Thyroid disease
- Autoimmune haemolytic anaemia
- CLL
Clinical presentation of ITP
- Easy bruising
- Epistaxis
- Menorrhagia
- Purpura
- Gum bleeding
- Major haemorrhage is rare
- Splenomegaly is rare
How is ITP diagnosed
- Bone marrow examination (increased megakaryocytes in marrow - thrombocytopenia)
- Platlet autoantibodies (not used for final diagnosis)
How is secondary ITP treated
- Corticosteroids
2. IV immunoglobulin (IgG)
Name a corticosteroid used to treat ITP
PREDNISOLONE
Why is IV IgG given
Raises platelet count more rapidly than steroids
Second line treatment for ITp
Splenectomy
If splenectomy fails - immunosuppression
What immunosuppression is given to ITP
ORAL AZATHIOPRINE
How is TTP (Thrombotic Thrombocytopenia Purport caused)
Widespread adhesion + aggregation of platelets leads to microvascular thrombosis + consumption of platelets = profound thrombocytopenia
Reduction in ADAMTS-13 (attacked by immune system)
Large multimers of vWF form resulting in platelets aggregation + fibrin deposition in small vessels = micro thrombi
Role of ADAMTS-13
Degradation of vWF
Causes of TTp
1, Idiopathic
- Autoimmune
- Cancer
- Pregnancy
- Drug-associated
Clinical presentation of TTP
- Purpura
- Fever
- Fluctuating cerebral dysfunction
- Haemolytic anaemia with red cell fragmentation accompanied by acute kidney injury
How is TTP treated
Plasma exchange to remove antibody to ADAMTS-13 as well as provide a source of ADAMTS-13
- IV METHYLPREDNISOLONE
- V RITUXIMAB
Does DIC occur in isolation
No
Why does DIC arise
Systemic activation of coagulation either by release of procoagulant material (e.g. tissue factor) or via cytokine pathways as part of the inflammatory response
Activation leads to widespread generation of fibrin and depositing in blood vessels = thrombosis + multi organ failure)
Also increases consumption of platelets + clotting factors and increased risk of bleeding
Causes of DIC
- Massive activation of coagulation cascade
- Initiating factors (extensive damage to vascular endothelium thereby exposing tissue factor + enhance expression of tissue factor by monocytes in response to cytokines)
- Sepsis
- Major trauma + tissue destruction
- Advanced cancer
- Obstetric complications
Clinical presentation of DIC
- Patient is acutely ill
2. Bleeding occurs from mouth, nose and venipuncture sites + widespread ecchymoses
What is ecchymoses
Discolouration of skin due to bleeding caused by bruising
Confusion
Bruising
Thrombotic events
Why does thrombotic events occur in DIC
- Vessel occlusion by fibrin and platelets - any organ may be involved but skin, brian and kidneys are most affected
How is DIC diagnosed
- Severe thrombocytopenia
- Diagnosis can be suggested from history
- Decreased fibrinogen
- Elevated FDPs (fibrin degradation products) - D-dimer
- PT, APTT, TT
What would blood films show in DIC
Fragmented RBCs
How is DIC treated
Treat underlying condition
Replace platlets via transfusion
FFP (fresh frozen plasma) to replace coagulation factors
Cryoprecipitate to replace fibrinogen + some coagulation factors
Red cell transfusion in patients who are bleeding
How does Heparin induce thrombocytopenia
- Heparin binds to a protein in th blood called PF4 (platelet factor IV) - forming Factor IV/Heparin
IgG binds to this complex forming IgG/PF4/Heparin which binds and activates platelets
Platelet consumption = thrombocytopenia/necoriss/thrombosis
Who are most at risk of heparin-induced thrombocytopenia
Cardiac Bypass surgery + unfractioned heparin treatment
How is Heprain-indcued thrombocytopenia diagnosed
Seen as a SHARP fall in platelets 5-19 days after Heparin treatment
How is Heparin-Induced thrombi treated
Immediatelyy stop heparin + start alternative anticoagulants
NEVER RE-EXPOSE to heparin
