Bleeding Disorders Flashcards
What is Disseminated Intravascular Coagulation (DIC)?
A condition where the inappropriate activation of the clotting cascade results in thrombosis formation and leads to depletion of clotting factors and platelets.
What are some causes of DIC?
- Secondary to Sepsis!
- Obstetric Emergencies
- Malignancy (Acute Promyelocytic Leukaemia)
- Hypovolaemic shock
What two methods result in activation of coagulation in DIC?
Either
- Release of procoagulant material (e.g. Tissue factor)
OR
- Via cytokine pathways as part of the inflammatory response.
What is generated to commence coagulation in DIC?
Widespread generation of fibrin and deposition in blood vessels, leading to thrombosis and multiorgan failure.
What happens to the Platelets and Coagulation factors in DIC?
The widespread coagulation uses them up.
What else is activated other than coagulation in DIC leading to the production of FDPs and D-Dimers.
There is Secondary Activation of Fibrinolysis.
What are FDPs and D-Dimers?
Fibrin Degradation Products and D-Dimers are both little chunks of broken up fibrin.
- Only get D-dimers from the breakdown of Clots.
What are the resulting consequences of coagulation activation and secondary action of Fibrinolysis?
A mixture of, Initial Thrombosis, Followed by a bleeding tendency due to consumption of coagulation factors and dysregulated fibrinolytic activation.
What does the Microvascular Thrombus formation manifest as?
End Organ Failure.
What does the Clotting factor consumption manifest as clinically?
Bruising, Purpura, Generalised Bleeding.
What is the Typical Clinical Presentation of DIC?
Patient is often acutely unwell and shocked.
Clinical presentation varies from no bleeding, to Profound haemostatic failure with widespread haemorrhage.
What symptoms would a patient with DIC exhibit?
Epistaxis, Gingival bleeding, Haematuria, Bleeding from cannula sites.
- Fever
- Confusion
- Potential Coma
What signs are common in DIC?
- Petechiae
- Bruising
- Confusion
- Hypotension.
What would the PT, APTT and TT usually show in DIC?
Usually very prolonged.
What is seen on Blood tests in DIC?
High levels of FDPs, including D-Dimers.
Severe Thrombocytopenia.
Blood film may show fragmented RBCs.
What is the management in DIC?
Treat underlying cause.
Supportive care
- Transfusions of platelets or clotting factors.
- Anticoagulation therapy may be necessary.
What is Haemophilia?
Hereditary disorder in which abnormally prolonged bleeding recurs episodically at one or a few sites on each occasion.
What is the genetic inheritance pattern in Haemophilia?
X-Linked recessive
What is Haemophilia A a deficiency of?
Factor VIII
(5x more common than Haemophilia B)
What is Haemophilia B a deficiency of?
Factor IX
Is there an abnormality of primary haemostasis in Haemophilia?
No
Where does bleeding usually occur in Haemophilia?
Bleeding from medium to large blood vessels, most commonly into joints.
What determines the severity of Haemophilia in Families?
Depends on Factor VIII/IX level involved.
How do patients with Mild Haemophilia usually present ?
Bleeding is usually only associated with injury or surgery so diagnosis is often made quite late in life.
What are some clinical features of severe haemophilia?
- Recurrent Haemarthroses
- Recurrent soft tissue bleeding. (Bruising in toddlers)
- Prolonged bleeding after dental extractions, surgeries etc..
What is seen on PT, APTT and TT in patients with Haemophillia?
An Isolated prolonged APTT.
What kind of test can be done to isolate the factor deficiency in Haemophilia?
Coagulation factor assays.
What can be used in Acute episodes of bleeding or prevention of excessive bleeding during surgery in patients with Haemophilia?
- Desmopressin For minor bleeds (Stimulates release of VWF)
- Infusions of Affected factor (VIII or IX) for major bleeds.
- Antifibrinolytics (Tranexamic Acid) are useful for bleeding wounds.
When should Antifibrinolytics (Tranexamic Acid) be avoided in Haemophilia Tx?
In muscle Haematomas, Haemarthrosis and Urinary bleeding as they can lead to fibrosis.
For Severe Haemophilia, Deficient factors can be replaced via IV infusions either as prophylaxis or in response to bleeding. What is a potential complication of this treatment?
The formation of antibodies against the clotting factor resulting in Tx becoming ineffective.
What is Haemophilia with inhibitors? And how is it Treated?
1/3 of Boys w Haemophilia A will develop an inhibitor to factor VIII following Infusions.
- Treatment should be directed by a specialist centre.
What immunisations are important in Haemophilia?
Hep B
What is Von-Willebrand’s Disease?
An inherited bleeding disorder characterised by a reduced quantity or function of VWF.
What is the primary cause of VWD?
A genetic mutation that results in deficiency or dysfunction of VWF.
- VWF gene located on Chromosome 12 (lots of mutations been identified)
What role does VWF play in Haemostasis?
Has a critical role as an adhesive protein in the platelet vessel wall interaction. The absence of this leads to impaired platelet adhesion and failure to create the platelet plug.
What deficiency can reduced VWF levels also lead to?
Deficiency in Factor VIII as it is not protected from premature degradation.
What clinical features are seen in Von-Willebrand’s Disease?
Range from Mild to more severe bleeding:
- Excess or prolonged bleeding from wounds.
- Excess or prolonged bleeding post-op.
- Easy Bruising
- Menorrhagia.
- Epistaxis.
- GI bleeding.
What would an FBC show in VWD?
May be normal or show microcytic anaemia.
NORMAL platelet count.
What would APTT, PT and TT show in VWD?
APPT may be normal or prolonged if factor VIII deficiency is present.
PT will be normal.
What can be tested for in VWD investigations?
VWF antigen test.
Factor VIII clotting activity test.
Specialist VWF testing e.g. VWF multimer test.
What is the management of VWD?
Depends on Severity.
- May involve Desmopressin.
- Plasma-derived Factor VIII concentrated containing intact VWF are mainstay of replacement therapy.
(Used to Tx bleeding or in surgery, or those who do not respond adequately to Desmopressin)
What is Immune thrombocytopenic purpura?
A syndrome where there is a decreased number of circulating platelets which leads to a bleeding tendency.
How can ITP occur?
May occur in isolation (primary ITP) or associated with other disorders (secondary)
What are some causes of Secondary ITP?
- Other autoimmune disorders (Anti-Phospholipid antibody syndrome and SLE)
- Viral Infections (CMV, VZV, Hep C and HIV)
- Infection with H.Pylori
- Medications
- Lymphoproliferative disorders
What is the Pathophysiology of ITP?
Caused by a type 2 hypersensitivity reaction:
- It is caused by the production of antibodies that target and destroy platelets.
- This can happen spontaneously, or it can be triggered by something, such as a viral infection.
What sort of Symptoms can ITP cause in otherwise healthy patients?
- Petechiae
- Ecchymoses
- Purpura
- Bleeding from venepuncture sites (nose, etc..)
What is Ecchymoses?
A bruise
What are purpura?
Purple spots or patches on your skin or mucous membranes.
What age does ITP usually present?
Under 10.
(often with a recent history of recent viral illness)
What would a blood test show in ITP?
Isolated Thrombocytopenia.
(no other findings)
- If something appears abnormal a bone marrow examination would likely be next course of action.
What is the management of ITP?
Usually no TX required and patients are monitored until platelets return to normal.
(~70% of patients will return to normal within 3 months)
When would intervention be needed in ITP?
- What intervention would be indicated?
If the patient is actively bleeding or severe thrombocytopenia (Platelets <10)
- Prednisolone
- IV Immunogobulins
- Blood transfusions if required
- Platelet Transfusions only work temporarily.
What is thrombotic Thrombocytopenia Purpura (TTP)?
Rare form of thrombotic microangiopathic haemolysis, thrombocytopenia and neurological abnormalities.
What is the aetiology of TTP?
Occurs due to a deficiency of metalloproteinase ADAMTS13.
- Can be a hereditary congenital mutation or due to autoimmune inhibition.
What sorts of triggers is TTP associated with?
- Medications
- AIDS
- Malignancy
What is the classical pentad for TTP presentation?
- Fever
- Microangiopathic Haemolytic anaemia (MAHA)
- Thrombocytopenic purpura
- CNS involvement: Headache, Confusion, Seizures.
- AKI
What would a FBC of a patient with TTP show?
Normocytic anaemia (secondary to haemolysis), Thrombocytopenia, and possibly a raised neutrophil count.
What would U&E show in a patient with TTP?
Raised Urea and Creatinine.
What would be seen on a blood film of a patient with TTP?
- Schistocytes (consistent with haemolysis).
- An elevated Retic count.
Which other common bloods would be elevated in TTP?
LFT
LDH
D-dimer
Indirect bilirubin
Haptoglobins would be low.
What helps differentiate between DIC and TTP?
Coagulation screen in TTP will be normal.
(Prolonged in DIC with low plasma fibrinogen)
What type of Assay is Diagnostic in TTP?
ADAMST13 assay
- Low ADAMST13 activity is diagnostic.
What would be seen on Urinalysis of a patient with TTP?
Proteinuria and Microscopic Haematuria.
What is the management of TTP?
- Fresh frozen plasma
- Plasma exchange
- High-dose steroids, low-dose aspirin and rituximab can also be given.
- Splenectomy may be used to Tx patients who do not respond to plasma exchange, or who relapse chronically.
What does Fresh frozen plasma contain in the context of TTP treatment?
Contains VWF-cleaving protease and complement components.
What does plasma exchange do in TTP?
Removes antibodies and toxins associated with the pathogenesis of the disease.
What is the first thing you should do on finding a major haemorrhage patient?
Trigger the major blood loss protocol.
What is the second step in the management of Massive Haemorrhage?
Take baseline blood samples before transfusion for:
- FBC, group and save, clotting screen.
What should be given to a patient with a massive haemorrhage as a result of trauma, who has presented within 3 hrs of the injury?
Tranexamic acid 1g bolus over 10 mins followed by IV infusion of 1g over 8 hrs.
What needs to be given in Massive Haemorrhage if Hb is Falling?
Red cells; Helps maintain tissue oxygenation.
What needs to be given in Massive Haemorrhage if PT ratio is >1.5?
FFP 15-20ml/Kg
- Replaces coagulation factors and helps to maintain coagulation close to normal.
What should be given in Massive Haemorrhage if Fibrinogen is <1.5g/L?
Cryoprecipitate (2 pools)
- Replaces Fibrinogen.
What should be given in Massive Haemorrhage if Platelets are <75x10^9/L?
Give Platelets 1 ATD.
- Helps correct thrombocytopenia.
