Bleeding Disorders

Question 1

What are the top differentials for abnormal bleeding?

Answer 1

Thrombocytopenia,
von Willebrand disease,
Haemophillia A or B,
DIC

Question 2

What are the causes of severe thrombocytopenia

Answer 2

ITP,
DIC,
TTP,
Haemtological malignancy

Question 3

What are causes of moderate thrombocytopenia?

Answer 3

Heparin induced thrombocytopenia,
Drug-induced,
Alcohol,
Liver disease,
Hypersplenism,
Viral infections,
Pregnancy,
SLE,
Vitamin B12

Question 4

What are causes of thrombocytopenia associated with reduced platelet production?

Answer 4

Viral infections eg, EBV, CMV and HIV.
B12 deficiency
Folic acid deficiency,
Liver failure causing reduced thrombopoietin,
Leukaemia,
Myelodysplastic syndrome,
Chemotherapy

Question 5

What are causes of thrombocytopenia associated with increased platelet destruction?

Answer 5

Medications eg, sodium valproate, methotrexate.
Alcohol,
Immune thrombocytopenic purpura,
Thrombotic thrombocytopenic purpura,
Heparin induced thrombocytopenia,
Haemolytic uraemic syndrome

Question 6

What is the presentation of thrombocytopenia?

Answer 6

Below 50 it may present with nose bleeds, bleeding gums, heavy periods, haematuria, rectal bleeding.
Below 10 it can present with intracranial haemorrhage and GI bleeding

Question 7

What is immune thrombocytopenic purpura?

Answer 7

Autoimmune disease where antibodies are targeted against the platelets.
Presents with non-blanching purpura.

Question 8

What is the management of ITP?

Answer 8

Prednisolone,
IV immunoglobulins,
Thrombopoietin receptor agonists,
Rituximab,
Splenectomy

Question 9

What is thrombotic thrombocytopenic purpura?

Answer 9

Tiny thombi form in vessels which causes microangiopathy. Caused inherited by defect in ADAMTS14 protein or antibodies are created against the protein. Diagnosis by looking at ADAMTS13 activity.

Question 10

What is the normal function of the ADAMTS13 protein?

Answer 10

inactivates von willebrand factor,
Reduces platelet adhesion to vessel walls,
Reduces clot formation

Question 11

What is the presentation of TTP?

Answer 11

Pentad to remember:
Fever,
Microagiopathic haemolytic anaemia,
Thrombocytopenic purpura,
CNS involvement (headaches, confusion, seizures)
AKI

Question 12

What is the management of TTP?

Answer 12

FFP,
Plasma exchange,
High dose steroids, low dose aspirin and rituximab.

Question 13

Describe features of heparin induced thrombocytopenia

Answer 13

Development of antibodies against platelets in response to heparin. This triggers clotting and so you get thrombosis. Think when patient is on heparin and clotting!!
Diagnosis - HIT antibodies.
Treatment - Stop heparin and use alternative

Question 14

What is von Willebrand disease and the different types

Answer 14

Autosomal dominant condition where there is defect in VWF (exposed when endothelial damage, causes platelets to bind and aggregate)
Type 1 - Partial deficiency of VWF (mildest and most common)
Type 2 - Reduced function of VWF.
Type 3 - Complete deficiency of VWF (most severe but rare type)

Question 15

Explain the extrinsic pathway of secondary haemostasis (initiation of the coagulation cascade)

Answer 15

Tissue factor binds to factor VII (7) activating it. Activated factor VII causes the activation of factor X (10). Activated factor 10 causes the activation factor V (5) which forms a complex with activated factor 10 and factor II (2 also known as prothombim) to form a prothombinase complex which causes the activation of factor 2 (prothombin to thrombin)
Factor IIa will go onto to activate fibrinogen into fibrin and factor XIII. Factor XIII then can cross link the fibrin which makes it stronger

Question 16

Explain the intrinsic pathway (propagation of the coagulation cascade)

Answer 16

The extrinsic pathway makes a small amount of thrombin which can go on to activate factor XI and factor VIII. Activated factor XI will activate factor IX. Now activated factors VIII and IX stimulate the prothombinase complex resulting in the formation of more thrombin.

Question 17

What is the presentation of von willebrand disease?

Answer 17

Nosebleeds,
Bleedign gums when brishing teeth,
Easy bruising,
Menorrhagia

Question 18

What are the investigations for von willebrand disease?

Answer 18

Prolonged bleeding time.
APTT may be prolonged.
Factor VIII levels reduced (Factor 8 degrades rapidly when not bound to WVF)
Defective platelet aggregation

Question 19

What is the management of von Willebrand disease?

Answer 19

Desmopressin (stimulates release of VWF from endothelium), This is first line.
Tranexamic acid,
Von Willebrand factor infusion +/- Factor VIII (in the context of heavy bleeding)
For heavy periods - TXA, mefenamic acid, mirena coil, COCP,

Question 20

Describe general features of haemophilia

Answer 20

Both are X-linked recessive disorders. Haemophilia A is deficiency in factor VIII (more common).
Haemophilia B is caused by a deficiency in factor IX.

Question 21

What is the presentation of Haemophilia?

Answer 21

Typically presents early in life with spontaneous bleeding into soft tissue, joints and muscle. This can present with haemarthrosis, compartment syndrome, nose bleeds, GI bleeding, haematuria

Question 22

What is the diagnosis and management of haemophilia?

Answer 22

Diagnosis - Bleeding scores, coagulation factor assays and genetic testing. Prolonged APTT but PT normal and thrombin time normal
Management - Give affected clotting factors as an IV infusion regularly or in response to bleeding. Risk of developing antibodies towards recombinant factors
Avoid TXA in haemarthrosis but can use in bleeding soft tissue wounds

Question 23

Describe disseminated intravascular coagulation and its causes

Answer 23

It is an acquired disease which causes microthrombi due to activation of the coag cascade and bleeding due to exhaustion of the coag cascade.
Caused by sepsis, malignancy, massive haemorrhage, severe trauma and pregnancy complications (pre-eclampsia, placental abruption, amniotic fluid embolism).

Question 24

What are the laboratory investigations for DIC?

Answer 24

PT and APTT are both prlonged, Fibrinogen reduced.
D-dimer
FBC, Platelets and blood film which shows RBC fragments (Due to fibrin which lays down in the vessel and cuts the RBCs as they travel past)

Question 25

What is the treatment for DIC?

Answer 25

Fresh frozen plasma +/- platelets if bleeding/high risk for bleeding.

Question 26

Name some examples of severe inherited platelet disorders

Answer 26

Glansmanns Thrombasthenia (normal platelet count bit absent/defective GP IIb/IIIa)
-Bernard Soulier Syndrome (Absent/defective GP Ib/V/IX and macrothrombocytopenia)
Both are rare autosomal recessive disorders with mucosal type bleeding pattern

Question 27

What are the coagulation results for a person on warfarin vs aspirin?

Answer 27

Warfarin: PT - prolonged. APTT - Normal, bleeding time normal.
Aspirin: PT - normal, APTT - normal, Bleeding time prolonged

Question 28

What is the pathophysiology of DIC?

Answer 28

Dysregulation of coagulation and fibrinolysis. Key factor is tissue factor. This is released in response to cytokines and TNF. Tissue factor binds to coagulation factors which then triggers the extrinsic pathway.