Bleeding Disorders Flashcards
State some differential diagnoses for abnormal or prolonged bleeding
- Thrombocytopenia
- Inherited clotting disorders
- Von Willebrand disease
- Haemophilia A
- Haemophilia B
- Disseminated intravascular coagulation
We can split causes of thrombocytopenia into problems with production and destruction. State some causes of thrombocytopenia due to problems with production
- Sepsis
- B12 deficiency
- Folate deficiency
- Liver failure (thrombopoietin is made in liver)
- Leukaemia
- Myelodysplastic syndrome
We can split causes of thrombocytopenia into problems with production and destruction. State some causes of thrombocytopenia due to destruction
- Medications (sodium valporate, methotrexate, PPIs, antihistamines)
- Alcohol
- Immune thrombocytopenic purpura
- Thrombotic thrombocytopenic purpura
- Heparin-induced thrombocytopenia
- Haemolytic-uraemic syndrome
Discuss potential presentations of thrombocytopenia
- Asymptomatic
- Easy bruising
- Easy and prolonged bleeding
- Nosebleeds
- Bleeding gums
- Heavy periods
- Blood in urine or stools
*NOTE: platelets <50x109 likely to present with bruising and prolonged bleeding times. Platelets <10x109 high risk for spontaneous bleeding e.g. intracranial or GI
Describe the pathophysiology immune thrombocytopenic purpura
*NOTE: immune thrombocytopenic purpura also known as autoimmune thrombocytopenic purpura, idiopathic thrombocytopenic purpura and primary thrombocytopenic purpura
- Body produces antibodies against platelets
- Causes an immune response against platelets
- Resulting in destruction of platelets
How is immune thrombocytopenic purpura likely to occur/present in children?
How is immune thrombocytopenic purpura likely to occur/present in adults?
Children: often triggered by infection & is self-limiting
Adults: more insidious onset and is chronic. More common in women. Often associated autoimmune condition.
What investigations would you do if you suspect immune thrombocytopenic purpura?
ITP is diagnosis of exclusion after ruled out other potential causes of thrombocytopenia. BMJ best practice say first investigations should be:
- FBC: low platelets
- Blood film: rule out pseudo thrombocytopenia caused by platelet aggregation when exposed to EDTA in sample collection tube
Discuss the management of immune thrombocytopenic purpura
- Corticosteroids (PO prednisolone)
- Adjunct: IV immunoglobulins
- Other options: immunosuppressive agents e.g. rituximab, splenectomy
- Education surrounding signs of bleeding (e.g. headaches, melena)
- Control of BP and menstrual periods if appropriate
Describe the pathophysiology of thrombotic thrombocytopenic purpura
- Congenital or acquired (due to autoimmune disease in which antibodies destroy protein) decrease of absence of ADAMTS 13 protein
- Protein usually breaks down/cleaves large multimers of von Willebrand factor and hence reduces platelet adhesion to vessel wall and thus reduces clot formation
- Shortage of protein results in small blood clots developing throughout small vessels in body
- Uses up platelets
- Causing thrombocytopenia
- Leading to bleeding
- Also causes haemolytic anaemia due to sheer stress on RBCs due to clots
How does thrombotic thrombocytopenia present?
- Thrombocytopenia
- Haemolytic anaemia
- Fever
- Renal failure
- Fluctuating neuro signs due to microemboli
What investigations would you do if you suspected thrombotic thrombocytopenic purpura?
- FBC
- Blood film (see schistocytes)
- Direct Coomb’s (rule out autoimmune haemolytic anaemia)
- U&Es (renal func)
- Urinalysis (damage to glomeruli can result in proteinuria)
- Haematinics (haptoglobin reduced)
State some treatment options for thrombotic thrombocytopenic purpura
- Plasma exchange
- Steroids
- Ritxuimab
Describe the pathophysiology of heparin induced thrombocytopenia
- Antibodies against platelets in response to exposure to heparin
- Occurs 2-14 days after exposure
- Heparin binds to platelet factor 4 which is found on inactivated platelets
- Heparin-PF4 complex is immunogenic in some people
- Body develops IgG antibodies against the complex
- Leads to destruction of platelets leading to thrombocytopenia (destroyed by spleen)
- However, binding of IgG antibodies to complex also causes activation of platelets; activated platelet releases mediators which activate other platelets
- Hence body is in hypercoagulable state and thrombosis occurs
Discuss the management of heparin induced thrombocytopenia
- Stop heparin
- Use alternative anticoagulation
What is the most common inherited bleeding disorder?
von Willebrand disease
For von Willebrand disease (VWD) state:
- Inheritance pattern
- How many types there are
- Autosomal dominant (MAJORITY)
- 3 types (type 3 most severe)
- Type 1: partial reduction in vWF
- Type 2: abnormal form of vWF
- Type 3: total lack of vWF
State some symptoms and signs of VWD
- Bleeding gums with brushing
- Nose bleeds
- Menorrhagia
- Heavy bleeding during surgery
What investigations would you do if you suspected VWD?
- FBC: normal in most pts
- Coagulation (PT, APTT): PT normal, APTT increased
- Factor VIII
*remember APTT measures intrinsic and PT measures extrinsic
Discuss the management of VWD
Often doesn’t require daily management, management often in response to major bleeding or trauma or in preparation for operations. Options:
- Desmopressin (stimulates release of vWF)
- VWF infusion
- Factor VIII infusion
Women may have the following to treat menorrhagia:
- Tranexamic acid
- COCP
- Mirena coil
- Norethisterone
- Hysterectomy is an option
What is the inheritance pattern of both haemophilia A and B?
X-linked recessive
Haemophilia A is a deficiency in…
Haemophilia B is a deficiency in…
- Haemophilia A: factor VIII
- Haemophilia B: factor IX
State some signs & symptoms of haemophilia
Severe bleeding disorders in which pts are at risk of excessive bleeding in response to minor trauma or spontaneous bleeding. Most cases present in neonates or early childhood. May present with:
- Cord bleeding in neonates
- Intracranial haemorrhage
- Haematoma
- Spontaneous haemarthrosis
- Abnormal bleeding in other areas e.g. gums, GI, urinary tract, following procedures
What investigations would you do if you suspect haemophilia?
- FBC: rule out thrombocytopenia
- Coagulation: for APTT and PT
- Factor VIII assay
- Factor IX assay
What results would you expect, in terms of APTT and PT, in haemophilia A and haemophilia B?
- Prolonged APTT
- Normal PT
Discuss the management of haemophilia
- Infusions of affected factor (can be prophylactically or in response to bleeding)
- Desmopressin (stimulate vWF release)
- Antifibrinolytics e.g. tranexamic acid
- Advice e.g. avoid contact sports, avoid NSAIDs etc…
*NOTE: pts can develop antibodies against the clotting factor resulting in treatment being no longer effective
State some potential causes of DIC
- Sepsis
- Malignancy
- Trauma
- Obstetric complications
- Severe immunological reactions e.g. blood transfusion reactions, transplant rejection
Describe the pathophysiology of DIC
- Usually coagulation and fibrinolysis are balanced
- In DIC, procoagulants (e.g. tissue factor) increase coagulation pathway resulting in widespread clotting
- Widespread clotting results in clotting factors being used up hence bleeding also occurs
- Furthermore, fibrin degradation products interfere with clot formation further worsening bleeding
“Disseminated intravascular coagulation (DIC) is an acquired syndrome characterised by activation of coagulation pathways, resulting in formation of intravascular thrombi and depletion of platelets and coagulation factors.” BMJ BEST PRACTICE
State some signs & symptoms of DIC
Could be anything related to bleeding or thrombosis
- Generalised bleeding in at least 3 unrelated sites is highly suggestive
- Petechiae, ecchymosis
- Haematuria
- Systemic signs of circulatory collapse (e.g. tachycardia, hypotension, cold extremities)
- Signs of microvascular thrombi e.g. gangrene, acral cyanosis, purpura fulminans
- CNS deficits e.g. altered consciousness
What investigations would you do if you suspect DIC?
- FBC: low platelets
- Coagulation studies: see separate FC
*If did blood film may also see Schistocytes due to microangiopathic haemolytic anaemia
What results would you expect from coagulation studies on DIC patient?
- Prolonged APTT
- Prolonged PT
- Decreased fibrinogen
- Increased fibrin degradation products e.g. D-dimer
Discuss the management of DIC
- Treatment of underlying disorder
- FFP
- Cryoprecipitate second line alternative (teach me surgery says if fibrinogen is <1g/L)
- Platelet infusion (if <20x109 or <50x109 with active bleeding)
State some potential complications of DIC
- Life threatening haemorrhage
- AKI
- Gangrene and loss of digits
- Cardiac tamonade
