Bleeding disorders Flashcards
1
Q
What are the 2 most common compents of the normal haemstatic system to have a problem in it ?
A
- Primary haemostasis - formation of platelet plug
- Secondary haemostasis - formation of fibrin clot
2
Q
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)
A
- 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
3
Q
What are the main congenital defects which cause vascular defects resulting in failure of primary haemostasis ?
A
Connective tissue disorders e.g. Marfans syndrome, Ehler danlos syndrome
4
Q
What is the more common causes of vascular defects/abnormalities resulting in failure of primary haemostasis ?
A
Acquired abnormalities:
- Vasculitis e.g. Henoch-scholein purpura
- Senile purpura
- Steroids
- Scurvey
5
Q
What are the signs/symptoms of marfans syndrome ?
A
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
6
Q
What are the signs/symptoms of ehler danlos syndrome ?
A
- 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
7
Q
What is the typical presentation of senile purpura ?
A
- Affects older people
- Chacterised by recurrent formation of bruises after mild trauma on the extensor surfaces
8
Q
What are the characteristic features of henoch-schonlein purpura?
A
- 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)
9
Q
What are the main causes of thrombocytopenia ?
A
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
10
Q
What is ITP
A
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
11
Q
Who is most commonly affected by ITP ?
A
- Usually children 2 weeks after an infection
- Or mainly seen in women
12
Q
What are the 2 main ways ITP can present?
A
- Acute - lasting 6-8 weeks
- Chronic lasting > 12 months
13
Q
What are the signs/symptoms of ITP ?
A
- Some children may have no symptoms at all
- Most common symptoms are bleeding, purpura, epitaxis & menorrhagia
14
Q
What are the investigations which should be done for someone suspected of having ITP ?
A
FBC & blood film - there should be no evidence of abnormalities other than platelets < 100x109
15
Q
What is the treatment of ITP ?
A
Mild symptoms - no tx needed
If severe bleeding symptoms e.g. mucosal bleeding or platelets < 20x109 then tx = prednisolone
16
Q
Describe the pathology of TTP
A
- 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)
17
Q
What are the clinical features of TTP?
A
All have MAHA (microangiopathic haemolytic anaemia) & thrombocytopenia
Additional features:
- AKI
- Fluctuating CNS signs (e.g. seizures, hemiparesis, decreased conciousness, decreased vision)
- Fever
18
Q
What are the causes of TTP?
A
- post-infection e.g. urinary, gastrointestinal (bloody diarrhoea)
- pregnancy
- drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir
- tumours
- SLE
- HIV
19
Q
What is the management of TTP?
A
It is an emergency get help
- 1st line = urgent plasma exchage
- 2nd line = steroids
20
Q
How is TTP diagnosed?
A
Same as for HUS
21
Q
What is HUS and its causes ?
A
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
22
Q
What are the clinical features of HUS?
A
Triad of:
- AKI (usually worse AKI than in TTP)
- Microangiopathic haemolytic anaemia (MAHA)
- Thrombocytopenia
23
Q
How is HUS investigated ?
A
- FBC showing - anaemia, thrombocytopaenia, fragmented blood film (schistocytes)
- Clotting tests are normal
- U&E: acute kidney injury
- stool culture
24
Q
What is the treatment of HUS ?
A
- 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
25
What are the causes of poor platelet function ?
1. Mainly drugs (anti-platelets) e.g. aspirin, NSAID's (also has a similar function to aspirin)
2. 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
26
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
27
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)
28
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
29
What are the 2 main ways in which fibrin clot failure can arise ?
1. Multiple clotting factor deficiencies e.g. DIC (note DIC causes decreased platelets & clotting factor def. hence mentioned in both primary & secondary haemostatic disorders)
2. Single clotting factor deficiencies e.g. haemophilia
30
What are the main causes of multiple clotting factor deficiencies ?
1. Liver failure
2. Vit K def./warfarin therapy
3. Complex coagulopathy - DIC
31
What 2 tests will both be prolonged in multiple clotting factor deficiences ?
PT & APTT
32
Where are all the clotting factors synthesised ?
In hepatocytes in the liver (hence in liver failure you can get decreased clotting factor sythesis)
33
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
34
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
35
Where is vit K absorbed & what is required for its absorption ?
Absorbed in the uppper intestine, requires bile salts for its absorption
36
What type of vitamin is vit K ? (or what is the solubility of it)
It is a fat soluble vitamin
37
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
38
What are the signs/symptoms of liver failure ?
* Nausea & vomiting
* RUQ pain
* Jaundice
* Fatigue & weight loss
* Strong alcohol history, hepatitis
39
What are the signs/symptoms of malabsorption?
* Diarrhoea
* Decreased weight
* Lethargy
* Steatorrhoea
40
What are some of the causes of GI malabsorption (which can inturn lead to vit K def.)?
1. Decreased bile - primary biliary cirrhosis, ileal ressection, biliary obstruction
2. Pancreatic insufficiency e.g. caused by pancreatic cancer, CF
41
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
42
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
43
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
44
What are the causes of DIC ?
* Major trauma/burns
* organ destruction
* Sepsis/severe infection
* Hypovolaemic shock
* Obstetric emergencies e.g. placental abruption
* Malignancy
45
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)
46
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
47
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.
48
How is vit K def treated ?
IV vit K + if acute haemorrhage give factor concentrate (2, 7, 9 & 10)
49
What is haemophilia /
An x-linked recessive condition which results in abnormally prolonged bleeding
50
What is the 2 types of haemophilia & the clotting factor def. they cause & state which is more common ?
1. Haemophilia A - due to factor VIII def. (5x's more common)
2. Haemophilia B - due to factor IX def.
Note - both behave clinically the same
51
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
52
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
53
What can the recurrent haemarthrosis result in, in haemophilia?
Arthropathy & joint deformity
54
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
55
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
