123 Inherited Deficiencies of Coagulation Factors II, V, V+VIII, VII, X, XI, and XIII Flashcards
Factor _____ and factor _____ deficiency are rare but occur relatively frequently compared to other factor deficiencies (apart from hemophilia A and B), whereas the other deficiencies are very rare
Factor XI and factor VII
7-11
The rarest rare blood disorders are
Factor II (prothrombin) and Combined factors V and VIII deficiency
Are the most frequent gene abnormalities, representing 50% to 80% of all identified mutations, except for LMAN1 variants where insertions/deletions are most frequent
Missense mutations
Main treatments for rare bleeding disorders
- Replacement therapy of deficient coagulation factor
- Nontransfusional adjuvant therapies (antifibrinolytic amino acids, estrogen/progestin)
- Fresh-frozen plasma
- Cryoprecipitate
Difficult due to lack of longitudinal clinical data and limitations of available laboratory assays
Requires considering patient’s personal and familial history of bleeding to guide management
Contain uncontrolled amounts of factor II, factor VII, and factor X, still often used for treatment of factor X deficiency
Prothrombin complex concentrates
No Factor V!
TRUE OR FALSE
Inherited deficiency of a coagulation factor does not protect patients from thrombosis.
TRUE
Inherited deficiency of a coagulation factor does not protect patients from thrombosis.
Inherited disorder presenting as type I (true deficiency) or type II (dysfunctional prothrombin)
PROTHROMBIN (FACTOR II) DEFICIENCY
- The activated partial thromboplastin time (aPTT) and prothrombin time (PT) are prolonged. The thrombin time (TT) is normal.
Types of prothrombin deficiency
* Severe (less than 5%)
* Moderate (5-10%)
* Mild (greater than 10%)
Factor with the longest half life
Factor XIII
9-12 days
Hereditary disorder characterized by concomitant deficiency of factor V activity and antigen (type I) or normal antigen levels with dysfunctional protein (type II)
Factor V deficiency
Factor V is synthesized in the liver and megakaryocytes/platelets
Autosomal dominant disorder with reduced platelet factor V levels due to enhanced proteolysis from overexpression of urokinase-type plasminogen activator
Quebec platelet disorder
caused by null mutations in the endoplasmic reticulum–Golgi intermediate compartment (ERGIC)-53 gene, now called the LMAN1 gene or **MCFD2 genes **
COMBINED DEFICIENCY OF FACTORS V AND VIII
The diagnosis is suggested by a prolonged PT with a normal aPTT.
one and only
FACTOR VII DEFICIENCY
May occur in patients with primary amyloidosis due to selective binding of this factor to amyloid fibrils or to the presence of an abnormal form of this factor.
Acquired factor X deficiency
Factor essential for the activation by thrombin of thrombin-activatable fibrinolysis inhibitor (TAFI) or carboxypeptidase B, an enzyme that inhibits fibrinolysis.
Deficiency may result in increased fibrinolytic activity, with consequent increase in bleeding.
Factor XI
Most patients with factor XI deficiency are Jewish.
Factor XI Displays both procoagulant and antifibrinolytic activities
The only RBD in which the EN-RBD study showed no association between clinical bleeding severity and coagulation factor activity level
Factor XI deficiency
