Chapter 26: Coagulation Disorders

Question 1

What is the most common of the hereditary clotting factor deficiencies?

Answer 1

Haemophillia A

Question 2

Fill in the blanks. “ Haemophillia A is caused by a deficiency of _________.”

Answer 2

Factor VIII ( 8)

Question 3

On which chromosome is Factor VIII located?

Answer 3

It is located on the long arm of the X chromosome.

Question 4

What are the clinical features of Haemophilia A?

Answer 4

• Infants may develop profuse post-circumcision haemorrhage or joint and soft tissue bleeds and excessive bruising when they start to be active.
• Recurrent painful haemarthroses ( bleeding into joint spaces) and muscle haematomas.
• Entrapment neuropathy or ischaemic necrosis.

*Spontaneous haematuria and gastrointestinal haemorrhage.

• Spontaneous intracerebral haemorrhage

Question 5

How are Haemophilic pseudotumours best visualised?

Answer 5

Magnetic resonance imaging (MRI

Question 6

What are the laboratory findings of Haemophilia A?

Answer 6

Abnormal Test Results:
1 Activated partial thromboplastin time (APTT).
2 Factor VIII clotting assay.

The platelet function analysis-100 (PFA-100) and prothrombin time (PT) are NORMAL.

Question 7

What are Haemophillic pseudotumurs?

Answer 7

Haemophilic pseudotumours are large encapsulated haematomas with progressive cystic swelling from repeated haemorrhage.

Question 8

Which drug is a bispecific monoclonal antibody that binds factors IX and X resulting in activation of factor X?

Answer 8

Emicizumab

Question 9

What is the main treatment for Haemophilia A?

Answer 9

This is treated with factor VIII replacement therapy, and spontaneous bleeding is usually controlled if the patient’s factor VIII level is raised to 30–50% of normal.

Question 10

What is the name given to the drug that also provides an alternative means of increasing the plasma factor VIII level in milder haemophiliacs?

Answer 10

1-Diamino-8-D-arginine vasopressin (DDAVP; desmo pressin)

Question 11

There is an impaired Ristocetin-induced platelet aggregation in which disease?

Answer 11

von Willebrand disease

Question 12

Fill in the blanks. “ The main site for haemorrhage in Hemophilia A and B is ___________ and the main site for Haemorrhage in von Willebrand disease is ___________.”

Answer 12

Haemophilia A & B - Muscle, joints, post-trauma or postoperative.

Von Wilebrand disease - Mucous membranes, skin cuts, post-trauma or postoperative.

Question 13

True or False? Factor VIII is may be moderately reduced in von Wilebrand disease.

Answer 13

TRUE!!!

Question 14

Which test is Prolonged in Haemophilia A, B and von Willebrand disease?

Answer 14

Partial Thromboplastin Time (PTT)

Question 15

Fill in the blanks. “ Following the release of the DDAVP drug there is a two- to fourfold rise maximum at 30–60 minutes in the patient’s own factor VIII by release of von Willebrand factor (VWF) from ________.”

Answer 15

Endothelial cells

Question 16

What are the laboratory findings for von Willebrand disease?

Answer 16

1. The PFA-100 test (see p. 310) is abnormal. Factor VIII levels are often low. If low, a factor VIII/VWF binding assay is
   performed.
2. The APTT may be prolonged.
3. VWF antigen levels are usually low. The sites of the mutations underlying the four subtypes of VWD.
4. There is defective platelet aggregation by patient plasma in the presence of ristocetin (VWF: Rco). Aggregation to other agents – adenosine diphosphate (ADP), thrombin or adrenaline – is usually normal. Other types of assay for VWF platelet binding are more frequently being used to avoid the variability and labour intensive ristocetin cofactor
   assay and reported as VWF: Ac for VWF activity.
5. Collagen-binding function (VWF: CB) is usually reduced (but rarely measured).
6. Multimer analysis is useful for diagnosing different sub- types.
7. The platelet count is normal except for type 2B disease.

Question 17

Where is Von Willebrand Factor produced?

Answer 17

VWF is produced in endothelial cells and megakaryocytes.

Question 18

True or False? Von Wilebrand disease is an Autosomal recessive disorder?

Answer 18

FALSE!! It is Autosomal Dominant

Question 19

True or False? In Von Wilebrand disease, Women are more severely affected than men at a given VWF level.

Answer 19

TRUE!!

Question 20

What is the most common inherited bleeding disorder?

Answer 20

Von Willebrand disease

Question 21

What are the clinical features of Von Wilebrand disease?

Answer 21

*Epistaxes
* Menorrhagia
* Excessive blood loss from superficial cuts and abrasions
*Operative and post-traumatic haemorrhage.
* Haemarthroses and muscle haematomas are rare, except in type 3 disease

Question 22

What is a classical clinical feature of Type 3 VWD?

Answer 22

Haemarthroses and muscle haematomas

Question 23

What are the different sub-types of VWD?

Answer 23

Type 1: Quantitative partial deficiency
Type 2: Functional abnormality
Type 3: Complete deficiency

Question 24

Which factor deficiency is seen in mainly Ashkenazi Jews and occurs in either sex?

Answer 24

Factor XI Deficiency

Question 25

What is the treatment for patient sixth Von Wilebrand disease?

Answer 25

1. Local measures and antifibrinolytic agent (e.g. tranexamic acid for mild bleeding).
2. DDAVP infusion for those with mild to moderate type 1 VWD. This releases VWF from endothelial cells 30 min-
   utes after intravenous infusion.
   3 High-purity VWF concentrates for patients with very low VWF levels. Plasma-derived factor VIII/VWF concentrates are used. Recombinant VWF is also available.

Question 26

What is the treatment for Factor XI deficiency ?

Answer 26

• Fibrinolytic inhibitor
• Factor XI concentrate
• Fresh frozen plasma (FFP)

Question 27

Which factor deficiency has a characteristic of a umbilical stump bleeding?

Answer 27

Factor XIII

Question 28

Where is Vitamin K derived from?

Answer 28

Green vegetables and bacterial synthesis in the gut.

Question 29

Haemorrhagic disease of the newborn is as a result of which deficiency?

Answer 29

Vitamin K deficiency

Question 30

What is the pathogenesis of Vitamin K deficiency?

Answer 30

Deficiency of vitamin K is caused by an inadequate diet, malabsorption or inhibition of vitamin K by vitamin K antagonist drugs such as warfarin.

Question 31

Fill in the blanks. “ Warfarin is associated with a decrease in the functional activity of factors of __________.”

Answer 31

Factors :
II
VII
IX
X
Protein C
Protein S

Question 32

What is the name of the enzyme that is inhibited by Warfarin?

Answer 32

Vitamin K epoxide reductase

Question 33

What is the Diagnosis of Haemorrhagic Disease of the newborn?

Answer 33

• The PT and APTT are both abnormal.
• The platelet count and fibrinogen are normal with absent fibrin degradation products.

Question 34

What is the treatment for bleeding infants with vitamin K deficiency?

Answer 34

• Vitamin K 1mg intramuscularly is given every 6 hours with, initially,

*Prothrombin complex concentrate if haemorrhage is severe.

Question 35

What is the diagnosis of Vitamin K deficiency in children and adults?

Answer 35

• Both PT and APTT are prolonged.

*There are low plasma levels of factors II, VII, IX and X.

Question 36

Which Factor has the shortest half -life?

Answer 36

Factor VII ( 6 hours)

Question 37

What is the treatment for Vitamin K deficiency in children and adults?

Answer 37

1. Prophylaxis: vitamin K 5 mg/day orally.
2. Active bleeding or prior to liver biopsy: vitamin K 10mg slowly intravenously. Some correction of PT is usual within 6 hours. The dose should be repeated on the next 2 days, after which optimal correction is usual.
3. Rapid correction may be achieved by infusion of prothrombin complex concentrate.

Question 38

What is the pathogenesis of Disseminated intravascular coagulation ( DIC)?

Answer 38

The key event underlying DIC is increased activity of thrombin in the circulation that overwhelms its normal rate of removal by natural anticoagulants

Question 39

What are the vascular abnormalities that can cause DIC?

Answer 39

Kasabach–Merritt syndrome
Leaking prosthetic valves
Cardiac bypass surgery
Vascular aneurysms

Question 40

What are the Obstretic complications that can cause DIC?

Answer 40

Amniotic fluid embolism
Premature separation of placenta
Eclampsia; retained placenta
Septic abortion

Question 41

Fill in the blanks. “ ___________ & __________ are malignancies that can result in DIC.”

Answer 41

Widespread mucin-secreting adenocarcinoma
Acute promyelocytic leukaemia

Question 42

What are the infections that can cause DIC?

Answer 42

• Gram-negative and meningococcal septicaemia
• Clostridium welchii septicaemia
• Severe falciparum malaria
• Viral infection – varicella, HIV, hepatitis, cytomegalovirus

Question 43

Bleeding, particularly from venepuncture sites or wounds is associated with which pathology?

Answer 43

Disseminated intravascular coagulation (DIC)

Question 43

What is the mnemonic associated with the causes of DIC?

Answer 43

“SSSTOP Making New Thrombi”

*S- heat Stroke
* S- Snake bites
*S- Sepsis (gram ⊝)
* T- Trauma
*O- Obstetric complications
* P - acute Pancreatitis
* Making - Malignancy
*New- Nephrotic syndrome
* Thrombi - Transfusion

Question 44

What are the clinical features of DIC?

Answer 44

• Bleeding, particularly from venepuncture sites or wounds.
• Generalized bleeding in the gastrointestinal tract, the oropharynx, into the lungs, urogenital tract and, in obstetric cases, vaginal bleed- ing may be particularly severe.
• Microthrombi may cause skin lesions
• Renal failure
• Gangrene of the fingers or toes
• Cerebral ischaemia

Question 45

What are the Laboratory findings of DIC?

Answer 45

1. The platelet count is low.
2. Fibrinogen concentration is low.
3. The thrombin time is prolonged.
4. High levels of fibrin degradation products such as D-dimers are found in serum and urine.
5. The PT and APTT are prolonged in the acute syndromes.
6. Compensation by the liver in chronic DIC may render some of the coagulation tests normal.
7. Decrease in factors V and VIII.

Question 46

What are the cells found in DIC?

Answer 46

Schistocytes due to microangiopathic haemolytic anaemia