Chapter 26: Coagulation Disorders Flashcards
What is the most common of the hereditary clotting factor deficiencies?
Haemophillia A
Fill in the blanks. “ Haemophillia A is caused by a deficiency of _________.”
Factor VIII ( 8)
On which chromosome is Factor VIII located?
It is located on the long arm of the X chromosome.
What are the clinical features of Haemophilia A?
- 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
How are Haemophilic pseudotumours best visualised?
Magnetic resonance imaging (MRI
What are the laboratory findings of Haemophilia A?
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.
What are Haemophillic pseudotumurs?
Haemophilic pseudotumours are large encapsulated haematomas with progressive cystic swelling from repeated haemorrhage.
Which drug is a bispecific monoclonal antibody that binds factors IX and X resulting in activation of factor X?
Emicizumab
What is the main treatment for Haemophilia A?
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.
What is the name given to the drug that also provides an alternative means of increasing the plasma factor VIII level in milder haemophiliacs?
1-Diamino-8-D-arginine vasopressin (DDAVP; desmo pressin)
There is an impaired Ristocetin-induced platelet aggregation in which disease?
von Willebrand disease
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 ___________.”
Haemophilia A & B - Muscle, joints, post-trauma or postoperative.
Von Wilebrand disease - Mucous membranes, skin cuts, post-trauma or postoperative.
True or False? Factor VIII is may be moderately reduced in von Wilebrand disease.
TRUE!!!
Which test is Prolonged in Haemophilia A, B and von Willebrand disease?
Partial Thromboplastin Time (PTT)
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 ________.”
Endothelial cells
What are the laboratory findings for von Willebrand disease?
- 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. - The APTT may be prolonged.
- VWF antigen levels are usually low. The sites of the mutations underlying the four subtypes of VWD.
- 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. - Collagen-binding function (VWF: CB) is usually reduced (but rarely measured).
- Multimer analysis is useful for diagnosing different sub- types.
- The platelet count is normal except for type 2B disease.
Where is Von Willebrand Factor produced?
VWF is produced in endothelial cells and megakaryocytes.
True or False? Von Wilebrand disease is an Autosomal recessive disorder?
FALSE!! It is Autosomal Dominant
True or False? In Von Wilebrand disease, Women are more severely affected than men at a given VWF level.
TRUE!!
What is the most common inherited bleeding disorder?
Von Willebrand disease
What are the clinical features of Von Wilebrand disease?
*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
What is a classical clinical feature of Type 3 VWD?
Haemarthroses and muscle haematomas
What are the different sub-types of VWD?
Type 1: Quantitative partial deficiency
Type 2: Functional abnormality
Type 3: Complete deficiency
Which factor deficiency is seen in mainly Ashkenazi Jews and occurs in either sex?
Factor XI Deficiency
What is the treatment for patient sixth Von Wilebrand disease?
- Local measures and antifibrinolytic agent (e.g. tranexamic acid for mild bleeding).
- 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.
What is the treatment for Factor XI deficiency ?
- Fibrinolytic inhibitor
- Factor XI concentrate
- Fresh frozen plasma (FFP)
Which factor deficiency has a characteristic of a umbilical stump bleeding?
Factor XIII
Where is Vitamin K derived from?
Green vegetables and bacterial synthesis in the gut.
Haemorrhagic disease of the newborn is as a result of which deficiency?
Vitamin K deficiency
What is the pathogenesis of Vitamin K deficiency?
Deficiency of vitamin K is caused by an inadequate diet, malabsorption or inhibition of vitamin K by vitamin K antagonist drugs such as warfarin.
Fill in the blanks. “ Warfarin is associated with a decrease in the functional activity of factors of __________.”
Factors :
II
VII
IX
X
Protein C
Protein S
What is the name of the enzyme that is inhibited by Warfarin?
Vitamin K epoxide reductase
What is the Diagnosis of Haemorrhagic Disease of the newborn?
- The PT and APTT are both abnormal.
- The platelet count and fibrinogen are normal with absent fibrin degradation products.
What is the treatment for bleeding infants with vitamin K deficiency?
- Vitamin K 1mg intramuscularly is given every 6 hours with, initially,
*Prothrombin complex concentrate if haemorrhage is severe.
What is the diagnosis of Vitamin K deficiency in children and adults?
- Both PT and APTT are prolonged.
*There are low plasma levels of factors II, VII, IX and X.
Which Factor has the shortest half -life?
Factor VII ( 6 hours)
What is the treatment for Vitamin K deficiency in children and adults?
- Prophylaxis: vitamin K 5 mg/day orally.
- 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.
- Rapid correction may be achieved by infusion of prothrombin complex concentrate.
What is the pathogenesis of Disseminated intravascular coagulation ( DIC)?
The key event underlying DIC is increased activity of thrombin in the circulation that overwhelms its normal rate of removal by natural anticoagulants
What are the vascular abnormalities that can cause DIC?
Kasabach–Merritt syndrome
Leaking prosthetic valves
Cardiac bypass surgery
Vascular aneurysms
What are the Obstretic complications that can cause DIC?
Amniotic fluid embolism
Premature separation of placenta
Eclampsia; retained placenta
Septic abortion
Fill in the blanks. “ ___________ & __________ are malignancies that can result in DIC.”
Widespread mucin-secreting adenocarcinoma
Acute promyelocytic leukaemia
What are the infections that can cause DIC?
- Gram-negative and meningococcal septicaemia
- Clostridium welchii septicaemia
- Severe falciparum malaria
- Viral infection – varicella, HIV, hepatitis, cytomegalovirus
Bleeding, particularly from venepuncture sites or wounds is associated with which pathology?
Disseminated intravascular coagulation (DIC)
What is the mnemonic associated with the causes of DIC?
“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
What are the clinical features of DIC?
- 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
What are the Laboratory findings of DIC?
- The platelet count is low.
- Fibrinogen concentration is low.
- The thrombin time is prolonged.
- High levels of fibrin degradation products such as D-dimers are found in serum and urine.
- The PT and APTT are prolonged in the acute syndromes.
- Compensation by the liver in chronic DIC may render some of the coagulation tests normal.
- Decrease in factors V and VIII.
What are the cells found in DIC?
Schistocytes due to microangiopathic haemolytic anaemia
