Coagulation disorders- amanda Flashcards
What are the two major categories of coagulation disorders?
- hereditary
-acquired
What do heridatory coagulation disorders involve?
Hereditary deficiencies of the coagulation factors
Give examples of hereditary coagulation disorders.
- FVIII-Haemophilia A
- FIX- haemophilia B
- VWF-Von Willebrand disease
-FXI- haemophilia C/Rosenthal’s disease - FXII
What is Haemophilia A?
-most common inherited coagulation disorder
- results from deficiency in factor VIII
- occurrence= 1:10,000 males
-development of PCR-based rapid screening and sequencing method led to identification of mutations in majority of haemophilia patients including:
— large deletions, missense, frameshift, splicing and insertional mutations in the FVIII gene
—half of all severe disease is due to a major inversion that often occur during male gametogenesis
—can occur very rarely in females due to marriage of a carrier to an affected male, often a cousin
What is haemophilia A described in females with?
Turner’s syndrome
What is the inheritance pattern of haemophilia A?
- X-linked
- but can result from recent or spontaneous mutation in patients without a family history
- occur almost exclusively in males
Clinical features of haemophilia A in infants?
-prolonged umbilical cord bleeding
-post circumcision haemorrhage
-excessive bruising particularly as mobility increases
Soft tissue and joint bleeds
What are clinical features of haemophilia A in adults/older children?
-recurrent haemarthrosis
-muscle haematomas
-progressive joint disability and deformity if untreated
-prolonged bleeding after dental extractions
-haematuria and gastrointestinal haemorrhage with obstruction as a result of intra-mucosal bleeding
What is haemarthrosis?
Haemorrhage into joint space
Clinical features (CONTD)
-Operative and post traumatic haemorrhage in severely and mildly affected patients are life-threatening
-In patients with severe disease, spontaneous intracerebral haemorrhage is an important cause of death
-Thrombocytopenia e.g. from HIV infection may intensify bleeding episodes in haemophiliacs
-There is correlation of the coagulation factor activity and the disease severity (see previous table)
Lab tests and findings
-Prothrombin time (PT) – Assesses Extrinsic and common pathway
-Activated partial thromboplastin time (APTT) – Assesses Intrinsic and common pathway
-Factor VIII clotting assay
-Analysis of platelet function
—PFA-100
—Bleeding time
How do we detect a carrier?
-DNA probes are used
-facilitates the Identification of a known specific mutation
-at 8-10 weeks gestation, chorionic biopsies provide adequate foetal DNA for analysis
- antenatal diagnosis: possible following low levels of factor VIII in foetal blood at 16-20 weeks (use of ultrasound-guided needle aspiration)
Treatment haemophilia A?
-factor VIII replacement therapy for bleeding episodes
- for post traumatic bleeding, major surgery or in case of haemorrhage occurrence at a dangerous site
- levels of FVIII should be raised to 100% and maintained above 50% when acute bleeding has stopped until the occurrence of healing
-recombinant factor VIII and plasma-derived purified factor VIII preparations are available for clinical use
What is DDAVP treatment for haemophilia A?
- alternative for plasma factor VIII
-DDAVP;desmopressin used in mild haemophiliacs only to stop bleeding
-administered intravenously or nasally
-2-4 fold rise in patient’s own factor VIII release at 30-60 minutes
Acquired coagulation disorders are more common than inherited ones. True or false
True
Describe acquired coagulation disorders
-involves multiple clotting factor deficiencies
-bleeding disorder/symptoms are not due to heriditary abnormalities
-secondary to other disorders
-consists of varied and complex aetiologies
Give examples of acquired coagulation disorders.
- disseminated intravascular coagulation (DIC)
-liver disease
-vitamin k-dependent coagulation factors deficiency
-haemorrhagic disease of a newborn usually due to low levels of vitamin k
-acquired inhibitors of coagulation factors- acquired FV and protein S deficiency
Liver disease cause of bleeding
Reduced synthesis of coagulation factors and thrombopoeitin
Sepsis and shock cause of bleeding
Acute DIC
Disseminated intravascular coagulation (DIC)
-increased activity of thrombin in the circulation that overwhelms its normal anticoagulants
-DIC caused by excessive activation of coagulation and loss of control + localisation mechanisms
-massive trauma results in excess phospholipid exposure from damaged tissue and TF release
-increase the expression of TF during response to cytokine, IL-IB and TNF-a in sepsis and malignancy (APL-acute promyelocytic leukaemia)
How many patients with APL will develop a DIC?
80%
What are the clinical features of DIC?
-severe bleeding from venepuncture and thrombosis may occur
-microthrombi may cause renal failure, skin lesions, peripheral gangrene with swelling and discolouration of the skin of the feet
-generalised bleeding in the GI tract
-organ failure due to microvascular thrombosis common but usually unrecognised
How is DIC diagnosed?
-must be differentiated from other acquired disorders of Haemostasis
-liver disease
-microangiopathic haemolytic anaemia
-hyper fibrinolysis
-massive transfusion
DIC scoring system:
Does patient have an underlying disorder associated with overt DIC, Request platelet count, PT, fibrinogen , D-dimmers, Score global coagulation tests results <50, elevated FDPs, prolonged PT >6,
Based on a score equal to or greater than 5
What is the treatment for DIC?
- according to underlying cause
-bleeding and thrombotic problems managed differently - bleeding: fresh frozen plasma
-thrombosis: use of heparin or antiplatelet drugs to inhibit coagulation process
