Bleeding disorders Flashcards
What are the 2 most common compents of the normal haemstatic system to have a problem in it ?
- Primary haemostasis - formation of platelet plug
- Secondary haemostasis - formation of fibrin clot
What are the 3 things which can have a problem in them resulting in failure of platelet plug formation ? (think about the 3 things needed)
- Vascular defects
- Platelet disorders; reduced number (thrombocytopenia) or reduced function (most commonly due to anti-platelets e.g. aspirin, NSAID’s)
- Von willebrand factor; deficiency (most common) or abnormal function
What are the main congenital defects which cause vascular defects resulting in failure of primary haemostasis ?
Connective tissue disorders e.g. Marfans syndrome, Ehler danlos syndrome
What is the more common causes of vascular defects/abnormalities resulting in failure of primary haemostasis ?
Acquired abnormalities:
- Vasculitis e.g. Henoch-scholein purpura
- Senile purpura
- Steroids
- Scurvey
What are the signs/symptoms of marfans syndrome ?
Major signs:
- Lens dislocation
- Aortic dissection or dilatation
- Long spidery fingers (arachnodactyly)
- Armspan > height
- Pectus deformity
- Scloiosis
- Flatfeet (pes planus)
Minor signs:
- High arched palate
- Joint hypermobility
- Mitral valve prolapse
Also repeated pnemothroaces
What are the signs/symptoms of ehler danlos syndrome ?
- Joint hypermbolity
- Loose unstable joints that dislocate easily
- Fatigue
- Easy bruising (due to failure of platelet plug)
- Joint pain & clicking
- Stretchy skin, may break easily
What is the typical presentation of senile purpura ?
- Affects older people
- Chacterised by recurrent formation of bruises after mild trauma on the extensor surfaces
What are the characteristic features of henoch-schonlein purpura?
- Purpura (none blanching purple papules due to intradermal bleeding) these bruises mainly appear on the legs or bottom (one of the main symptoms of a primary haemostasis disorder)
- Usually occurs between ages 2-11 & affects boys > girls
- May get some joint pain & swelling, abdo pain +/- kidney disease (haematuria, renal failure) (dont think you get thrombocytopenia which is useful to differentiate from ITP)
What are the main causes of thrombocytopenia ?
Decreased marrow production:
- Aplastic anaemia
- Megablastic anaemia
- Marrow infiltration e.g. leukaemia, myeloma
- Marrow suppression e.g. chemo, radiotherapy
Excessive platelet destruction:
- DIC - disseminated intravscular coagulation
- ITP - immune thrombocytopenia
- Hypersplenism (covered in another lect.) - EBV, HIV are common causes
- TTP - thrombocytic thrombocytopenic purpura
What is ITP
This is an autoimmune disorder which results in thrombocytopenia due to anti-platelet antibodies
It is defined as a platelet count < 100x109 in the absence of other causes or disorders assocoated with thrombocytopenia:
- Absent systemic symptoms such as weight loss, fever, joiny pain (arthralgia), alopecia, venous thrombosis
- No splenomegaly or hepatomegaly
- No lymphadenopathy
- Absence of medicines that cause thrombocytopnia e.g. heparin, alcohol etc
Who is most commonly affected by ITP ?
- Usually children 2 weeks after an infection
- Or mainly seen in women
What are the 2 main ways ITP can present?
- Acute - lasting 6-8 weeks
- Chronic lasting > 12 months
What are the signs/symptoms of ITP ?
- Some children may have no symptoms at all
- Most common symptoms are bleeding, purpura, epitaxis & menorrhagia
What are the investigations which should be done for someone suspected of having ITP ?
FBC & blood film - there should be no evidence of abnormalities other than platelets < 100x109
What is the treatment of ITP ?
Mild symptoms - no tx needed
If severe bleeding symptoms e.g. mucosal bleeding or platelets < 20x109 then tx = prednisolone
Describe the pathology of TTP
- Abnormally large and sticky multimers of von Willebrand’s factor cause platelets to clump within vessels
- In TTP there is a deficiency of ADAMTS13 (a metalloprotease enzyme) which breakdowns (‘cleaves’) large multimers of von Willebrand’s factor
- Overlaps with haemolytic uraemic syndrome (HUS)
What are the clinical features of TTP?
All have MAHA (microangiopathic haemolytic anaemia) & thrombocytopenia
Additional features:
- AKI
- Fluctuating CNS signs (e.g. seizures, hemiparesis, decreased conciousness, decreased vision)
- Fever
What are the causes of TTP?
- post-infection e.g. urinary, gastrointestinal (bloody diarrhoea)
- pregnancy
- drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir
- tumours
- SLE
- HIV
What is the management of TTP?
It is an emergency get help
- 1st line = urgent plasma exchage
- 2nd line = steroids
How is TTP diagnosed?
Same as for HUS
What is HUS and its causes ?
It is generally seen in young children and is usually secondary to:
- classically Shiga toxin-producing Escherichia coli (STEC) 0157:H7 (‘verotoxigenic’, ‘enterohaemorrhagic’). This is the most common cause in children, accounting for over 90% of cases
- pneumococcal infection
- HIV
- Rare: SLE, drugs, cancer
What are the clinical features of HUS?
Triad of:
- AKI (usually worse AKI than in TTP)
- Microangiopathic haemolytic anaemia (MAHA)
- Thrombocytopenia
How is HUS investigated ?
- FBC showing - anaemia, thrombocytopaenia, fragmented blood film (schistocytes)
- Clotting tests are normal
- U&E: acute kidney injury
- stool culture
What is the treatment of HUS ?
- 1st line treatment is supportive e.g. Fluids, blood transfusion and dialysis if required (there is no role for antibiotics, despite the preceding diarrhoeal illness in many patients)
- The indications for plasma exchange in HUS are complicated. As a general rule plasma exchange is reserved for severe cases of HUS not associated with diarrhoea
What are the causes of poor platelet function ?
- Mainly drugs (anti-platelets) e.g. aspirin, NSAID’s (also has a similar function to aspirin)
- Renal failure - due to build up of toxins inhibiting platelet function
==> look out for symptoms of renal failure or people on drugs e.g. aspirin or NSAID’s who present with symptoms of primary haemostasis dysfunction
What is the inheritance of VWF deficiency ?
- Autosomal dominant
- Look out for a strong fam history of bleeding - history of increased menorrhagia & bleeding post e.g. dental extraction
What are the symptoms of VWF deficiency ?
They are the symptoms of a primary haemoastic problem & are generally mild in severity:
- Bruising
- Epitaxis
- Menorrhagia
- Increased bleeding post commonly tooth extraction (but also post-op bleeding increased)
What are the investigations used to diagnose VWF deficiency ?
- PT - normal
- APTT - prologned (due to VWF role with protecting VIII, therefore VIII is decreased causing prolongation)
- VWF antigen decreased
What are the 2 main ways in which fibrin clot failure can arise ?
- Multiple clotting factor deficiencies e.g. DIC (note DIC causes decreased platelets & clotting factor def. hence mentioned in both primary & secondary haemostatic disorders)
- Single clotting factor deficiencies e.g. haemophilia
What are the main causes of multiple clotting factor deficiencies ?
- Liver failure
- Vit K def./warfarin therapy
- Complex coagulopathy - DIC
What 2 tests will both be prolonged in multiple clotting factor deficiences ?
PT & APTT
Where are all the clotting factors synthesised ?
In hepatocytes in the liver (hence in liver failure you can get decreased clotting factor sythesis)
What clotting factors function depends on Vit K?
Factors II, VII, IX & X - they depend on Vit K carboxylating them
Note - the same factors are inhibited by warfarin
Describe where we get vit K from ?
We get vit K from our diet primarily from green leafy veg e.g. burssle sporuts, broccoli, kale & intestinal synthesis by bacteria
Where is vit K absorbed & what is required for its absorption ?
Absorbed in the uppper intestine, requires bile salts for its absorption
What type of vitamin is vit K ? (or what is the solubility of it)
It is a fat soluble vitamin
What are the causes of vit K deficiency ?
- Poor dietary intake
- Malabsorption
- Obstructive jaundice e.g. gallstone in common bile duct
- Vit K antagonists
- Haemorrhagic disease of the newborn
What are the signs/symptoms of liver failure ?
- Nausea & vomiting
- RUQ pain
- Jaundice
- Fatigue & weight loss
- Strong alcohol history, hepatitis
What are the signs/symptoms of malabsorption?
- Diarrhoea
- Decreased weight
- Lethargy
- Steatorrhoea
What are some of the causes of GI malabsorption (which can inturn lead to vit K def.)?
- Decreased bile - primary biliary cirrhosis, ileal ressection, biliary obstruction
- Pancreatic insufficiency e.g. caused by pancreatic cancer, CF
What is haemorrhagic disease of the newborn & why is it very uncommon now ?
- It is where there is bleeding in one or multiple areas e.g. umbilical stump, mucous membranes, GI tract, areas where struck by needle etc
- It is so uncommon because babies now given Vit K at birth
What is DIC?
- A condition which arises due to excessive & inappropriate activation of the coagulation system (primary, secondary & fibrinolysis)
- Causing formation of microvascular thrombus formation (in the small vessels)
- The thrombi formation may lead to vascular obstruction/ischaemia & multi-organ failure
- The formation of the microvascular thrombi resulting in depletion of platelets & clotting factors
What does the consumption of platelets & clotting factors in DIC result in ?
- Bruising, purpura & generalised bleeding - bleeding from at least 3 unrelated sites is very suggestive
- Hypotension, oliguria & tachycardia - signs of circulatory collapse
What are the causes of DIC ?
- Major trauma/burns
- organ destruction
- Sepsis/severe infection
- Hypovolaemic shock
- Obstetric emergencies e.g. placental abruption
- Malignancy
How is DIC diagnosed ?
- FBC - decreased platelets
- PT - prolonged
- APTT - prolonged (PT is usually prolonged first, APTT may not yet be prolonged because VIII has the shortest hald life ==> PT affected first)
- Fibrinogen - decreased massively
- D-dimer - increased (as all the clots forming will be getting broken down)
What is the treatment of DIC?
- Treat the underlying cause
- Replacement therapy - platelet transfusions, FFP for replacement of coag factors + fibrinogen replacement by giving cryoprecipitate when fibrinogen levels are low
How is vit K def. diagnosed?
- PT & APTT prolonged
- Test for high levels of des-gamma-carboxyprothrombin (DCP) this is high in vit K def.
How is vit K def treated ?
IV vit K + if acute haemorrhage give factor concentrate (2, 7, 9 & 10)
What is haemophilia /
An x-linked recessive condition which results in abnormally prolonged bleeding
What is the 2 types of haemophilia & the clotting factor def. they cause & state which is more common ?
- Haemophilia A - due to factor VIII def. (5x’s more common)
- Haemophilia B - due to factor IX def.
Note - both behave clinically the same
What is the typical presentation of haemophilia ?
- There is no problem with primary haemostasis
- Often presents with prolonged bleeding after dental extraction, surgery & invasive procedures
- HIstory of spontaneous bleeding into joints (haemarthrosis) esp into knees, ankles & elbows - this is very, very suggestive
- Soft tissue bleeding - bruising esp in toddlers
What is the typical presentation of haemophilia ?
- There is no problem with primary haemostasis
- Often presents with prolonged bleeding after dental extraction, surgery & invasive procedures
- HIstory of spontaneous bleeding into joints (haemarthrosis) esp into knees, ankles & elbows - this is very, very suggestive
- Soft tissue bleeding - bruising esp in toddlers
What can the recurrent haemarthrosis result in, in haemophilia?
Arthropathy & joint deformity
What are the investigations done to diagnose haemophilia?
- PT - normal
- APTT - prolonged
- Factor VIII & IX assay (as talking about A&B here) - VIII decreased in A, XI decreased in type B
What is the treatment of haemophilia ?
- Avoid NSAID’s & IM injections
- For minor bleeding - pressure & elevation + desmopressin
- Major bleeds e.g. haemarthrosis or lifethreatening - give factor concentrate VIII or IX
