Haemostasis Disorders Flashcards
What do haemostasis disorders cause?
Haemorrhage and/or thrombosis
What are the 3 main steps of haemostasis?
- Primary haemostasis = platelet plug
- Secondary haemostasis = fibrin plug that requires the coagulation cascade
- Clot lysis
What are these conditions called?
Left - >3mm ecchymoses
Right - <3mm petechiae
What are we likely to see with primary and secondary haemostasis problems?
Primary
* Petechiae/ecchymoses common
* Bleeding from mucous membranes
* Often more than one site of bleeding
* Haematomas rare
- Mucosal haemorrhage
- Prolonged bleeding at sites of injury
Secondary
* Petechiae/ecchymoses rare
* Deep or cavity bleeds
* Can bleed from mucous membranes
* Sometimes single site of bleeding
* Haematomas common
What is needed to make a platelet clot?
Cells: Platelets, endothelial cells (source of von Willebrand factor and inhibitors)
Proteins: von Willebrand factor (vWF) and others
Facilitators:Platelet agonists such as thrombin, collagen is also a platelet activator
Physiologic inhibitors: Nitric oxide, prostacyclin (prostaglandin E12) – these are produced by endothelial cells.
What does diascopy test? What does the answer mean?
Does the lesion blanch under a glass slide (or glass cup)?
YES – the skin redness is caused by vascular vasodilation and squashing the site removes/fades the lesions
NO – no fading of the lesion means that there is haemorrhage in the skin (petechiae)
What are the 3 mechanisms of primary haemostasis dysfunction?
Low platelet numbers: thrombocytopaenia
Platelet dysfunction: thrombocytopathia
vWF deficiency
How can you investigate primary haemostatic disorders?
- Signalment
- Platelet count and morphology
- Bleeding usually only seen if platelets <50 x109/L (reference approx. 150-500 x109/L)
- Buccal mucosal bleeding time (BMBT) - normal for greyhounds is 3.2 minutes, other dogs is 4 minutes and cats is 2 minutes
- Von Willebrand factor (VWF)
- Platelet function assays
What can cause thrombocytopaenia?
**Defective platelet production **
* Bone marrow neoplasia e.g. leukaemia
* Drug/chemical/toxin-induced BM suppression
* BM infections (especially viral and rickettsial)
Accelerated platelet removal
* Immune-mediated thrombocytopaenia (IMTP) (most common)
* Consumption in microangiopathic conditions (disseminated intravascular coagulation (DIC))
Platelet sequestration or loss
* Splenomegaly / vascular pooling
* Acute ongoing haemorrhage
What occurs in immune-mediated thrombocytopaenia? How is it categorised? What animals are most at risk?
Platelets destroyed in the circulation and tissues faster than they can be made in the bone marrow
IMTP can be categorised as:
* Primary – idiopathic
* Secondary – drug-induced, secondary to infection, neoplasia-related
Evans Syndrome = IMHA + IMTP
Signalment
Young to middle-aged female dogs are over-represented, especially Cocker spaniels, miniature/toy poodles and old English sheepdogs which are all specifically predisposed
How do we treat IMTP? How is it managed long term? What is the prognosis?
- Treat any underlying disease!
- Whole blood transfusion isn’t that useful for increasing platelet counts
- Acute and long-term treatment centres around immunosuppression: Dexamethasone; prednisolone; azathioprine; cyclosporin; mycophenolate mofetil
- Splenectomy has had variable results but could be considered in refractive cases
Follow up:
* Keep monitoring platelet counts, at least monthly
* Immunosuppressive therapy should be continued for a minimum of 4-6 months
Prognosis:
* Can be good, reported 10-15% mortality; relapse 10-40%
* Negative prognostic indicators: melaena; high blood urea (BUN)
What are causes of thrombocytopathia? How are they diagnosed?
- Inherited thrombopathias
- Drug-induced defects of platelet function – various, particularly NSAIDs
- Platelet dysplasia
- Myeloproliferative disease and other forms of neoplasia
Diagnosis
* Normal PLT count but prolonged BMBT
* Normal levels of vWF
* To a degree it is often a diagnosis of exclusion
* PLT function tests
How are thrombocytopathias treated?
- No specific therapy
- Platelet transfusions - Effect may be limited
- Withdraw any drugs e.g. NSAIDs
- Treat symptomatically e.g. blood transfusion if marked anaemia
What are the 3 types of vWD? What is the clinical severity of each?
I - Abnormally low concentrations of structurally normal vWF
* Milder / Variable
II - Structurally abnormal vWF
* Severe
III - Essentially no plasma vWF
* Diagnosed by ELISA
* Severe
Doberman
How is vWD diagnosed?
Clinical signs – typical of a primary haemostatic defect
* Mucosal haemorrhage, cutaneous bruising, prolonged bleeding from surgical and traumatic wounds
* Occasionally more profound bleeding
Diagnostic testing
* Platelet count will be normal
* BMBT is a useful screening test for vWD
* Diagnosis is confirmed by demonstration of low vWF antigen concentrations
* BUT the measurement does not always accurately predict the risk of haemorrhage
Genetic testing
How is vWD treated?
- Plasma in severe cases – stabilisation and cessation of active haemorrhage
- Cryoprecipitate
- Red cells if oxygen-carrying capacity compromised
Type 1 vWD treatment
* Desmopressin 1µg/kg SC in the dog
* Acts by causing release of vWF from endothelial cells
What is needed in secondary haemostasis?
Cells: Fibroblasts, platelets, endothelial cells, leukocytes
Enzymatic coagulation factors: Factors XI, X, IX, VII, and II
Non-enzymatic coagulation factors – cofactors: Tissue factor (TF), Factors V and VIII
Fibrinogen
Calcium
How is fibrinogen formed? Why is it used diagnostically?
End product of the coagulation cascade
* Soluble plasma glycoprotein, synthesised by the liver
* Converted by thrombin into fibrin during blood coagulation
* Fibrin is then cross-linked by factor XIII to form a clot
Why is fibrinogen used diagnostically?
* Elevated due to any form of inflammation (acute phase protein) – takes 24-48hrs, often before clinical signs
* Low levels can indicate systemic activation of clotting system (consumption of clotting factors)
- Fibrin degradation products (FDPs) – made from the breakdown of fibrinogen – indicate a pro-thrombotic state
How do we interpret increased or decreased fibrinogen concentration?
Fibrinogen decreased
* Indication of disseminated intravascular coagulation (DIC)
* Potential bleeding
* Liver problem
Fibrinogen increased
* Viral and bacterial infections
* Potential bleeding
* Kidney disease
* Liver problem
* Traumatic injuries, surgery
* Cancer
* Heart disease
* Canine pregnancy, post-abortion
What factors need vitamin K?
Factors II, VII, IX and X
What hapens clinically if secondary haemostasis is dysfunctional?
- haematomas
- epistaxis
- melena
- internal bleeding
How will blood look on an xray?
Soft tissue opacity
What tests can we run to check secondary haemostasis?
Whole blood clotting time (WBCT)
* Crude measure of the intrinsic and common pathways
* Also increased if thrombocytopaenia is present
Prothrombin time (PT) / one stage prothrombin time (OSPT)
* Measure of the extrinsic and common pathways
* PT is prolonged due to a significant deficiency of any one factor (<30% of its normal value)
Activated partial thromboplastin time (APTT) / partial thromboplastin time (PTT)
* Measure of the intrinsic and common pathways
* APTT is also prolonged due to marked deficiency of a single factor (<30% of its normal concentration)
Specific factor assays
* The level of some individual clotting factors can be measured
* This would most commonly be indicated in the investigation of inherited coagulation disorders
WHat are examples of congenital and acquired disorders of secondary haemostasis?
Congenital
* Haemophilia
* Factor VIII deficiency (Haemophilia A) and Factor IX deficiency (Haemophilia B)
* Sex-linked (males), spontaneous bleeding
* APTT increased; assay FVIII or FIX to confirm
Acquired
* Vitamin K antagonism
* Coumarin, rat bait, rodenticide toxicity
* Depletion of clotting factors II, VII, IX and X
* 1-3 days for clinical effects
* Hepatic disease
* Clotting factors and inhibitory factors produced in the liver. PT and APTT increased
What are key point in the management of any patient with a coagulopathy?
- Avoid subcutaneous injections
- Do not use intramuscular injections
- Minimise invasive procedures
- Handle gently
How is thrombosis diagnosed?
- Thrombosis itself can be hard to detect clinically -> causes hypoxia and tissue damage
- To test fibrinolysis -> fibrinogen and its degradation products (FDPs), as well fibrin breakdown products like D-dimer
- D-dimer increased whenever there is activation of thrombin (to create crosslinked fibrin) OR fibrinolysis = thrombosis AND fibrinolysis
- We can also test for levels of inhibitors – if antithrombin III is reduced in the plasma, there is a risk of thrombosis
What diseases can cause animals to be in a pro-thombotic state?
- DIC (increased D-dimers are a sensitive indicator)
- Feline thromboembolic disease
- Protein-losing nephropathy
- Hyperadrenocorticism
What occurs during DIC? What are the different phases?
Disseminated intravascular coagulation
- Excessive activation of haemostatic pathways -> high thrombin and microvascular thrombi
- Coagulation factors and platelets get “used up” -> haemorrhage
Phases
* Non-overt DIC (compensated) -> no clinically detectable abnormalities
- D-dimers will be increased and fibrinogen decreased
* As things get worse, the DIC may enter an “overt” phase -> haemorrhage and end-organ damage
What are triggers for DIC?
- endothelial damage (sepsis, heat stroke)
- platelet activation (viral)
- release of tissue procoagulants (trauma)
- infectious agents
- neoplasia
- inflammation
- intravascular haemolysis
How can you test for DIC?
- Thrombocytopenia (or dropping platelet count in the normal range)
- Hypofibrinogenaemia (coagulation factors get used up); high fibrinogen degradation products (D-dimer high)
- Schistocytes (RBC fragments: schistocytes but also keratocytes and acanthocytes; only 20% of dogs and 8% cats, also a non-specific finding)
