Bleeding disorders Flashcards
What is Henoch-Schonlein Purpura?
IgA vasculitis that presents with a purpuric rash affecting the lower limbs and buttocks in children. Inflammation occurs in the affected organs due to IgA deposits in the blood vessels
Henoch-Schonlein Purpura is often triggered by..
Upper airway infection or gastroenteritis
Four classic features of HSP are..
Purpura (100%)
Joint pain (75%)
Abdominal pain (50%)
Renal involvement (50%)
Abdominal pain in HSP can lead to..
Gastrointestinal haemorrhage, intussusception and bowel infarction
HSP affects the kidneys in around 50% of patients, causing..
IgA nephritis. Can lead to microscopic or macroscopic haematuria and proteinuria
T or F: If there is more than 2+ of protein on the urine dipstick the child has developed nephrotic syndrome and will have a degree of oedema
True
Ix for HSP
FBC + blood film
Renal profile
Tx for HSP
Analgesia for arthralgia
Nephropathy - supportive
Criteria for diagnosing HSP
EULAR/PRINTO/PRES criteria
Palpable purpura (not petichiae) + at least one of:
Diffuse abdominal pain
Arthritis or arthralgia
IgA deposits on histology (biopsy)
Proteinuria or haematuria
It is important that patients with HSP are monitored closely whilst the illness is active. They need close monitoring with repeated..
Urine dipstick monitoring for renal involvement
Blood pressure monitoring for hypertension
What is Thrombocytopenia?
Low platelet count
Reduced platelet production can occur with..
Certain viral infections (e.g., Epstein-Barr virus, cytomegalovirus and HIV)
B12 deficiency
Folic acid deficiency
Liver failure, causing reduced thrombopoietin production by the liver
Leukaemia
Myelodysplastic syndrome
Chemotherapy
Increased platelet destruction can occur with..
Sodium valproate and methotrexate
Alcohol
Immune thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Heparin-induced thrombocytopenia
Haemolytic uraemic syndrome
Platelet counts below 50 x 109/L will result in..
Easy bruising and prolonged bleeding times (nosebleeds, bleeding gums, heavy periods etc)
Platelet counts below 10 x 109/L are at high risk for..
Spontaneous bleeding:
Intracranial haemorrhage
Gastrointestinal bleeding
The top differentials of abnormal or prolonged bleeding to remember are..
Thrombocytopenia
Von Willebrand disease
Haemophilia A and haemophilia B
Disseminated intravascular coagulation (usually secondary to sepsis)
What is ITP?
Antibodies are created against glycoprotein IIb/IIIa or Ib-V-IX complex leading to thrombocytopenia
Characteristic of ITP
Purpura
Mx of ITP
Prednisolone
IV immunoglobulins
Thrombopoietin receptor agonists (e.g., avatrombopag)
Rituximab
Splenectomy
Children with ITP usually have an acute thrombocytopenia that may follow __________ or ____________. In contrast, adults tend to have a more __________ condition
Children with ITP usually have an acute thrombocytopenia that may follow infection or vaccination. In contrast, adults tend to have a more chronic condition
Epidemiology of ITP in adults
More common in older females
Ix for ITP in adults
Full blood count: isolated thrombocytopenia
Blood film
Mx for ITP in adults
Oral prednisolone
IVIG if active bleeding or an urgent invasive procedure is required
What is Evan’s syndrome?
ITP in association with autoimmune haemolytic anaemia (AIHA)
ITP in children is an example of which type of reaction?
Type II hypersensitivity reaction
Ix for ITP in children
FBC
Blood film
Bone marrow examination if there is lymph node enlargement/ splenomegaly, high/ low white cells failure to resolve/respond to treatment
Mx of ITP in children
Resolves within 6 months
Avoid activities that may result in trauma (e.g. team sports)
If platelet is very low then:
Oral/ IV corticosteroid
IV immunoglobulins
Platelet transfusions in an emergency (e.g. active bleeding) but only a temporary measure as they are soon destroyed by the circulating antibodies
Give examples of drugs that cause thrombocytopenia
Quinine
Abciximab
NSAIDs
Diuretics: furosemide
Antibiotics: penicillins, sulphonamides, rifampicin
Anticonvulsants: carbamazepine, valproate
heparin
If a patient with gestational ITP becomes dangerously thrombocytopenic, she will usually be treated with..
Steroids and a diagnosis of ITP assumed
Pregnant women found to have low platelets during a booking visit or those with a previous diagnosis of ITP may need to be tested for..
Serum antiplatelet antibodies for confirmation
Gestational thrombocytopenia does not affect the neonate, but ITP can do if..
Maternal antibodies cross the placenta
T or F: Depending on the degree of thrombocytopenia in the newborn, platelet transfusions may be indicated. Serial platelet counts can also be performed to see whether there is an inherited thrombocytopenia
True
What is Thrombotic Thrombocytopenic Purpura?
Tiny thrombi develop throughout the small vessels, using up platelets
In TTP, as the problem is in the small vessels, it is described as a microangiopathy. It causes..
Thrombocytopenia
Purpura
Tissue ischaemia and end-organ damage
Thrombi develop due to a problem with a specific protein called ADAMTS13. This protein normally..
Inactivates von Willebrand factor
Reduces platelet adhesion to vessel walls
Reduces clot formation
Deficiency in the ADAMTS13 protein can be due to..
An inherited genetic mutation (hereditary)
Autoimmune disease, where antibodies are created against the protein (acquired)
Thrombotic thrombocytopenic purpura overlaps with..
Haemolytic uraemic syndrome (HUS)
Fluctuating neuro signs (microemboli)
Microangiopathic haemolytic anaemia
Thrombocytopenia
Renal failure
Thrombotic thrombocytopenic purpura
Causes of TPP
Post-infection e.g. urinary, gastrointestinal
Pregnancy
Drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir
Tumours
SLE/HIV
In Heparin-Induced Thrombocytopenia, heparin targets a protein on platelets called..
Platelet factor 4 (PF4)
Physiology of HIT
HIT antibodies bind to platelets and activate the clotting system, causing a hypercoagulable state and thrombosis (e.g., deep vein thrombosis). They also break down platelets and cause thrombocytopenia
Ix of HIT
HIT antibodies on a blood sample
Tx of HIT
Stopping heparin and using an alternative anticoagulant guided by a specialist (e.g., fondaparinux or argatroban)
What is DIC?
Activation and release of TF which binds with coagulation factors that then triggers the extrinsic pathway (via Factor VII) which subsequently triggers the intrinsic pathway (XII to XI to IX) of coagulation
Causes of DIC
Sepsis and trauma
Obstetric complications e.g. aminiotic fluid embolism, HELLP
Malignancy
↓ platelets
↓ fibrinogen
↑ PT & APTT
↑ fibrinogen degradation products
schistocytes due to microangiopathic haemolytic anaemia
DIC
Prothrombin time: Prolonged
APTT: Normal
Bleeding time: Normal
Platelet count: Normal
Warfarin administration
Prothrombin time: Normal
APTT: Normal
Bleeding time: Pronlonged
Platelet count: Normal
Aspirin administration
Prothrombin time: Often normal (may be prolonged)
APTT: Prolonged
Bleeding time: Normal
Platelet count: Normal
Heparin
Prothrombin time: Prolonged
APTT: Prolonged
Bleeding time: Prolonged
Platelet count: Low
DIC
Von Willebrand disease mode of inheritance
Autosomal dominant
Von Willebrand disease can also occur secondary to..
Underlying disease (e.g., leukaemia)
Von Willebrand factor is important in..
Platelet adhesion and aggregation in damaged vessels
What are the three types of VWF?
1: partial deficiency of VWF and is the most common and mildest type
2: reduced function of VWF
3: involves a complete deficiency of VWF and is the most rare and severe type
History of unusually easy, prolonged or heavy bleeding:
Bleeding gums with brushing
Nosebleeds (epistaxis)
Easy bruising
Heavy menstrual bleeding (menorrhagia)
Heavy bleeding during and after surgical operations
VWF
Ix for VWF
History of abnormal bleeding, family history, bleeding assessment tools and laboratory investigations
Mx of VWF
In response to significant bleeding:
Desmopressin (stimulates the release of vWF from endothelial cells)
Tranexamic acid
Von Willebrand factor infusion
Factor VIII plus von Willebrand factor infusion
Haemophilia mode of inheritance
X-linked recessive disorder of coagulation
Haemophilia A is due to a deficiency of factor ____ whilst in haemophilia B (Christmas disease) there is a lack of factor ____
Haemophilia A is due to a deficiency of factor VIII whilst in haemophilia B (Christmas disease) there is a lack of factor IX
Haemoarthroses
Haematomas
Prolonged bleeding after surgery or trauma
Haemophilia
Ix for Haemophilia
Prolonged APTT
Bleeding time, thrombin time, prothrombin time normal
Tx for Haemophilia
The affected clotting factors (VIII or IX) can be given by intravenous infusion, either regularly or in response to bleeding
Up to 10-15% of patients with haemophilia A develop antibodies to..
Factor VIII treatment
____________ is the commonest cause of primary haemostatic failure
Thrombocytopenia
Multiple factor deficiencies that affect secondary haemostasis
Liver failure
Vitamin K Deficiency/Warfarin therapy
DIC
Factors ___________ are carboxylated by vitamin K which is essential for function
II, VII, IX & X
Where is Vit. K absorbed?
Upper intestine
Requires bile salts for absorption
What causes Vit. K deficiency?
Poor dietary intake
Malabsorption
Obstructive jaundice
Vitamin K antagonists (warfarin)
Haemorrhagic disease of the newborn
