Bleeding Disorders (including thrombocytopenia)

Question 1

What is thrombocytopenia?

Answer 1

Thrombocytopenia describes a low platelet count. The normal platelet count is between 150 to 450 x 109/L. There are a long list of causes of a low platelet count. They can be split into problems with production or destruction.

Question 2

problems with production

Answer 2

Sepsis
B12 or folic acid deficiency
Liver failure causing reduced thrombopoietin production in the liver
Leukaemia
Myelodysplastic syndrome

Question 3

Problems with destruction

Answer 3

Medications (sodium valproate, methotrexate, isotretinoin, antihistamines, proton pump inhibitors)
Alcohol
Immune thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Heparin induced thrombocytopenia
Haemolytic-uraemic syndrome

Question 4

Presentation

Answer 4

A mild thrombocytopenia may be asymptomatic and found incidentally on a full blood count.

Platelet counts below 50 x 109/L will result in easy or spontaneous bruising and prolonged bleeding times. They may present with nosebleeds, bleeding gums, heavy periods, easy bruising or blood in the urine or stools.

Platelet counts below 10 x 109/L are high risk for spontaneous bleeding. Spontaneous intracranial haemorrhage or GI bleeds are particularly concerning.

Question 5

DDx of abnormal or prolonged bleeding

Answer 5

Thrombocytopenia (low platelets)
Haemophilia A and haemophilia B
Von Willebrand Disease
Disseminated intravascular coagulation (usually secondary to sepsis)

Question 6

What is immune thrombocytopenia purpura

Answer 6

ITP is a condition where antibodies are created against platelets. This causes an immune response against platelets, resulting in the destruction of platelets and a low platelet count.

Question 7

How to manage immune thrombocytopenia purpura?

Answer 7

Prednisolone (steroids)
IV immunoglobulins
Rituximab (a monoclonal antibody against B cells)
Splenectomy

The platelet count needs to be monitored and the patient needs education about concerning signs of bleeding such as persistent headaches and melaena and when to seek help. Additional measures such as carefully controlling blood pressure and suppressing menstrual periods are also important.

Question 8

What is thrombotic thrombocytopenia purpura?

Answer 8

This is a condition where tiny blood clots develop throughout the small vessels of the body using up platelets and causing thrombocytopenia, bleeding under the skin and other systemic issues. It affect the small vessels so it is described as a microangiopathy.

Question 9

Why do blood clots develop in thrombotic thrombocytopenia purpura?

Answer 9

The blood clots develop due to a problem with a specific protein called ADAMTS13. This protein normally inactivates von Willebrand factor and reduces platelet adhesion to vessel walls and clot formation. A shortage in this protein leads to von Willebrand factor overactivity and the formation of blood clots in small vessels. This causes platelets to be used up leading to thrombocytopenia. The blood clots in the small vessels break up red blood cells, leading to haemolytic anaemia.

Question 10

What can ADAMTS13 protein deficiency be due to

Answer 10

due to an inherited genetic mutation or due to autoimmune disease where antibodies are created against the protein.

Question 11

treatment for thrombotic thrombocytopenia purpura?

Answer 11

plasma exchange, steroids and rituximab (a monoclonal antibody against B cells).

Question 12

What is heparin induced thrombocytopenia?

Answer 12

Heparin induced thrombocytopenia (HIT) involves the development of antibodies against platelets in response to exposure to heparin. These heparin induced antibodies specifically target a protein on the platelets called platelet factor 4 (PF4). These are anti-PF4/heparin antibodies.

Question 13

What causes heparin induced thrombocytopenia?

Answer 13

The HIT antibodies bind to platelets and activate clotting mechanisms. This causes a hypercoagulable state and leads to thrombosis. They also break down platelets and cause thrombocytopenia. Therefore there is an unintuitive situation where a patient on heparin with low platelets forms unexpected blood clots.

Question 14

HOw to test for heparin induced thrombocytopenia?

Answer 14

Diagnosis is by testing for the HIT antibodies in the patients blood.

Question 15

How to manage heparin induced thrombocytopenia?

Answer 15

Management is by stopping heparin and using an alternative anticoagulant guided by a specialist.

Question 16

VWD- What is von willebrand disease?

Answer 16

most common inherited cause of abnormal bleeding (haemophilia). There are many different underlying genetic causes, most of which are autosomal dominant. The causes involve a deficiency, absence or malfunctioning of a glycoprotein called von Willebrand factor (VWF). There are three types based on the underlying cause and ranging from type 1 to type 3. Type 3 is the most severe.

Question 17

VWD- presentation

Answer 17

Patients present with a history of unusually easy, prolonged or heavy bleeding:

Bleeding gums with brushing
Nose bleeds (epistaxis)
Heavy menstrual bleeding (menorrhagia)
Heavy bleeding during surgical operations
Family history of heavy bleeding or von Willebrand disease is very relevant.

Question 18

VWD- diagnosis

Answer 18

Diagnosis is based on a history of abnormal bleeding, family history, bleeding assessment tools and laboratory investigations. Due to all the underlying causes there is no easy von Willebrand disease test. This can make diagnosis challenging and beyond the scope of most medical exams.

Question 19

VWD - management

Answer 19

Von Willebrand disease does not require day to day treatment. Management is required either in response to major bleeding or trauma (to stop bleeding) or in preparation for operations (to prevent bleeding):

Desmopressin can be used to stimulates the release of VWF
VWF can be infused
Factor VIII is often infused along with plasma derived VWF
Women with VWD that suffer with heavy periods can be managed by a combination of:

Tranexamic acid
Mefanamic acid
Norethisterone
Combined oral contraceptive pill
Mirena coil
Hysterectomy may be required in severe cases

Question 20

H- what causes haemophilia a?

Answer 20

Haemophilia A is caused by a deficiency in factor VIII

Question 21

H- what causes haemophilia b?

Answer 21

Haemophilia B (also known as Christmas disease) is caused by a deficiency in factor IX.

Question 22

H- what are haemophilia a and b genetically?

Answer 22

Both haemophilia A and B are X linked recessive. This means in order to have the condition all of the X chromosomes need to have the abnormal gene

almost exclusively affect males.

Question 23

H- S+S

Answer 23

Patients can bleed excessively in response to minor trauma and are also at risk of spontaneous haemorrhage without any trauma.
Most cases present in neonates or early childhood. It can present with intracranial haemorrhage, haematomas and cord bleeding in neonates.
Spontaneous bleeding into joints (haemoathrosis) and muscles are a classic feature of severe haemophilia and worth remembering for your exams. If untreated this can lead to joint damage and deformity.

Question 24

H- Where can abnormal bleeding also occur (less characteristic)?

Answer 24

Gums
Gastrointestinal tract
Urinary tract causing haematuria
Retroperitoneal space
Intracranial
Following procedures

Question 25

H- diagnosis

Answer 25

bleeding scores, coagulation factor assays and genetic testing.

Question 26

H- management

Answer 26

The affected clotting factors (VIII or IX) can be replaced by intravenous infusions. This can be either prophylactically or in response to bleeding. A complication of this treatment is formation of antibodies against the clotting factor resulting in the treatment becoming ineffective.

Acute episodes of bleeding or prevention of excessive bleeding during surgical procedures involve:

Infusions of the affected factor (VIII or IX)
Desmopressin to stimulate the release of von Willebrand Factor
Antifibrinolytics such as tranexamic acid