Platelets + Disorders

Question 1

How are platelets formed

Answer 1

Formed by fragmentation of megakaryocytic cytoplasm in bone marrow

Question 2

Advantage of platelets having a disc shape

Answer 2

Allows them to flow close to the endothelium

Question 3

Lifespan of platelets

Answer 3

7-10 days

Question 4

How are platelets broken down

Answer 4

Phagocytksed by splenic macrophages in red pulp

Question 5

Where is thrombopoietin produced

Answer 5

Liver

Question 6

How does liver damage effect platelets

Answer 6

Reduced thrombopoietin = decreased platelets

Question 7

Compensatory mechanism for decreased TPO

Answer 7

More TPO able to bind to MK = increased platelet production

Question 8

What precursor molecule is Thromboxane A2 made from

Answer 8

Arachidonic acid via COX-1

Question 9

Role of Thromboxane A2

Answer 9

Induces platelet aggregation + vasoconstriction

Question 10

What molecule activates P2Y12

Answer 10

ADP

Question 11

Role of P2Y12

Answer 11

Amplifies activation of platelets + helps activate glycoprotein IIb/IIIa

Question 12

Role of IIb/IIIa

Answer 12

Receptor for fibrinogen and vWF

Question 13

What is vWF

Answer 13

clotting factor needed for platelets to adhere to damaged blood vessels

Question 14

Role of IIb/IIIa

Answer 14

Aids platelet adherence and aggregation

Question 15

What is vWF disease

Answer 15

reduced vWF activity = platelets are unable to bind to damaged blood vessels resulting in platelet dysfunction + muco-cutaneous bleeding

Question 16

What is thrombocytopenia

Answer 16

Deficiency of platelets in th blood

Question 17

What is congenital thrombocytopenia

Answer 17

1. Malfunctioning megakaryocytes in bone marrow

Question 18

What causes thrombocytopenia

Answer 18

1. Infiltration of bone marrow (leukaemia, metastatic malignancy, lymphoma, myeloma, myelofibrosis)
2. Reduced platelet production by bone marrow

Question 19

What can result in reduced platelet production by bone marrow = thrombcytopenia

Answer 19

1. Low B12/folate
2. Reduced TPO
3. Medication
4. Toxins
5. Infections
6. Aplastic anaemia

Question 20

What medication causes thrombocytopenia

Answer 20

1. Methotrexate

2. Chemotherapy

Question 21

4 ways increased DESTRUCTION of platelets = thrombocytopenia

Answer 21

1. Autoimmune (ITP)
2. Hypersplenism (portal hypertension + splenomegaly)
   Drug-related immune destruction (heparin induced thrombocytopenia)

Question 22

What disorders cause consumption of platelets

Answer 22

1. DIC

2. TTP

Question 23

How is ITP caused

Answer 23

Immune destruction by platelets

Antibody-coated platelets are removed following binding to Fc receptors on macrophages

IgG antibodies form to platelets and megakaryocytes

Question 24

Where is primary ITP more common

Answer 24

CHildren

Question 25

What age group does ITP mainly cause

Answer 25

2-6 years

Question 26

Onset of ITP

Answer 26

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)

Question 27

Is life-threatening haemorrhage common in ITP

Answer 27

No

Question 28

When does Secondary ITP occur (chronic)

Answer 28

In adults

Question 29

Gender does 2ndary ITP occur

Answer 29

Women

Question 30

What autoimmune conditions is Secondary ITP associated with

Answer 30

1. SLE 2. Thyroid disease 3. Autoimmune haemolytic anaemia 4. CLL

Question 31

Clinical presentation of ITP

Answer 31

1. Easy bruising 2. Epistaxis 3. Menorrhagia 4. Purpura 5. Gum bleeding 6. Major haemorrhage is rare 7. Splenomegaly is rare

Question 32

How is ITP diagnosed

Answer 32

1. Bone marrow examination (increased megakaryocytes in marrow - thrombocytopenia) 2. Platlet autoantibodies (not used for final diagnosis)

Question 33

How is secondary ITP treated

Answer 33

1. Corticosteroids | 2. IV immunoglobulin (IgG)

Question 34

Name a corticosteroid used to treat ITP

Answer 34

PREDNISOLONE

Question 35

Why is IV IgG given

Answer 35

Raises platelet count more rapidly than steroids

Question 36

Second line treatment for ITp

Answer 36

Splenectomy If splenectomy fails - immunosuppression

Question 37

What immunosuppression is given to ITP

Answer 37

ORAL AZATHIOPRINE

Question 38

How is TTP (Thrombotic Thrombocytopenia Purport caused)

Answer 38

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

Question 39

Role of ADAMTS-13

Answer 39

Degradation of vWF

Question 40

Causes of TTp

Answer 40

1, Idiopathic 2. Autoimmune 3. Cancer 4. Pregnancy 5. Drug-associated

Question 41

Clinical presentation of TTP

Answer 41

1. Purpura 2. Fever 3. Fluctuating cerebral dysfunction 4. Haemolytic anaemia with red cell fragmentation accompanied by acute kidney injury

Question 42

How is TTP treated

Answer 42

Plasma exchange to remove antibody to ADAMTS-13 as well as provide a source of ADAMTS-13 2. IV METHYLPREDNISOLONE 3. V RITUXIMAB

Question 43

Does DIC occur in isolation

Answer 43

No

Question 44

Why does DIC arise

Answer 44

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

Question 45

Causes of DIC

Answer 45

1. Massive activation of coagulation cascade 2. Initiating factors (extensive damage to vascular endothelium thereby exposing tissue factor + enhance expression of tissue factor by monocytes in response to cytokines) 3. Sepsis 4. Major trauma + tissue destruction 5. Advanced cancer 6. Obstetric complications

Question 46

Clinical presentation of DIC

Answer 46

1. Patient is acutely ill | 2. Bleeding occurs from mouth, nose and venipuncture sites + widespread ecchymoses

Question 47

What is ecchymoses

Answer 47

Discolouration of skin due to bleeding caused by bruising Confusion Bruising Thrombotic events

Question 48

Why does thrombotic events occur in DIC

Answer 48

1. Vessel occlusion by fibrin and platelets - any organ may be involved but skin, brian and kidneys are most affected

Question 49

How is DIC diagnosed

Answer 49

1. Severe thrombocytopenia 2. Diagnosis can be suggested from history 3. Decreased fibrinogen 4. Elevated FDPs (fibrin degradation products) - D-dimer 5. PT, APTT, TT

Question 50

What would blood films show in DIC

Answer 50

Fragmented RBCs

Question 51

How is DIC treated

Answer 51

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

Question 52

How does Heparin induce thrombocytopenia

Answer 52

1. 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

Question 53

Who are most at risk of heparin-induced thrombocytopenia

Answer 53

Cardiac Bypass surgery + unfractioned heparin treatment

Question 54

How is Heprain-indcued thrombocytopenia diagnosed

Answer 54

Seen as a SHARP fall in platelets 5-19 days after Heparin treatment

Question 55

How is Heparin-Induced thrombi treated

Answer 55

Immediatelyy stop heparin + start alternative anticoagulants NEVER RE-EXPOSE to heparin