polycythaemia rubra vera = - cause - effect

primary polycythaemia - Overactive bone marrow - no external cause. genetic mutation in JAK2 gene - Myeloproliferative disorder. - oversesntivie to EPO --> increased RBC production Increase in rbc, also in wbc and platelets

haem middle tier Flashcards by David Sog

polycythaemia =

types

too many rbc, HB high and high packed cell volume (cell part of blood)

opposite of anaemia

primary - polycythaemia rubra vera
secondary- rbc rise in order to compensate (Reactive)

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polycythaemia rubra vera =

cause
effect

primary polycythaemia

Overactive bone marrow
no external cause. genetic mutation in JAK2 gene
Myeloproliferative disorder.
oversesntivie to EPO –> increased RBC production

Increase in rbc, also in wbc and platelets

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secondary causes of polycythaemia

Increase in rbc to compensate/ reactive : …
High altitude
resp issue inc smoking, lung disease
heart issue
Anabolic steroid
EPO (erythropoeitin) taken
chronic hypoxia
abnormal rbc structure
stimulates bone marrow to make rbc

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signs of polycythaemia

hepato/splenomegaly
abnormal FBC
hypertension

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symptoms of polycythaemia

Plethoric = rosy cheeks, also hands and feet
Itching after hot bath
Effects of thrombus
easing brusing/bleeding
fatigue
hyperviscosity –> headaches, dizzy, vision impaired
tinnitus

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polycythaemia investigations

FBC (PCV, Hb, RBC) , blood film
bone marrow biopsy
genetic testing JAK2 gene (polycythaemia vera)
if this is negative, look for secondary cause
serum EPO = low(insitgates rbc production)

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polycythaemia management

Aspirin
Venesection (take blood)
Hydroxycarbamide (chemo)- suppresses bone marrow
allopurinol to reduce gout
radioactive phosphorus if over 70 but increases risk of leukaemia

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polycythaemia complications

Acute myeloid leukaemia

Thrombotic events -clots etc

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relative polycythaemia

Apparent polycytaemia

Chronic
Associated with obesity, hypertension, high intake of alcohol/ tobacco

Dehydration

Acute
Cause = dehydration eg alcohol , diuretics

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primary causes of polycythaemia

Mutations in EPO receptor
High oxygen affinity haemoglobins
polycythaemia vera

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disseminated intravascular coagulation causes inc cause pathophysiology

Secondary – NEVER occurs in isolation

Extensive damage to vascular endothelium so tissue factor is exposed
Tissue factor expression is enhanced by monocytes, in response to cytokines

Malignancy
Major trauma and tissue destructin
Infections, sepsis
Hemolytic transfusion reactions
Liver disease
Obstetric complications

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disseminated intravascualr coagulation phtophysiology

Thrombin (coagulation system) activated inappropriately
Clotting occurs inappropriately, widespread, until clotting factors are exhausted inc widespread fibrin generation and deposition.
This can cause microvascular thrombosis and so can lead to multiorgan failure (Esp kidneys and brain)….
At this point uncontrolled bleeding occurs due to the consumption of platelets
Aka Thrombosis followed by bleeding

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disseminated intravascular coagultion symptoms

Acute, 
Bleeding - shock
Nose 
Mouth
Venipuncture sites
Skin
- Purpura
- Petechiae
- Localised infarction
- Bruising 
Confusion
Fever
Organ effects due to thrombosis --- brain and kidneys especially

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dissemintated intravascular coagulation investigations

Long prothrombin time and other similar sounding times
Platelets v low
Fibrinogen low
High D dimer (fibrin degradation product)
Blood film = fragmented RBCs

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disseminated intravascular coagulation management

Treat underlying cause
Platelet transfusion
‘Fresh frozen plasma’ to replace the coagulation factors
Cryoprecipitate to replace fibrinogen and some coagulation factors
Red cell transfusion if patient is bleeding
Activated protein c

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over anti-coagulation bleeding risk factors/ causes

iatrogenic – excess use of anticoagulation therapy

inappropriate presecription of warfarin/ heparin
Cardiac bypass surgery - lots of heparin use
Unfractionated heparin treatment
bad compliance
polypharmacy

over anti-coagulation bleeding - heparin action and effects

Heparin binds to platelet factor 4 (a protein) to form a complex (PF4/Hepain)
IgG binds to this complex to form a new complex (IgG/PF4/Heparin)
This complex (IgG/PF4/Heparin) binds and activates platelets
So platelets are consumed, resulting in thrombocytopenia
Also - thrombosis and skin necrosis occurs

over anti-coagulation bleeding general pathophysiology

Excess use of anticoagulation therapy

Anticoagulation causes blood to inappropriately avoid clotting → bleeding

over anti-coagulation bleeding symptoms

Bleeding

Bruising
Melena (black poo - upper GI bleed)
Epistaxis (nose bleeds)
Haematemesis
Haemoptysis

over anti-coagulation bleeding investigations (heparin)

Sharp fall in platelets 5-10 days after starting heparin treatment

over anti-coagulation bleeding management

Vitamin k (phytomenadione) for warfarin
Protamine sulphate for heparin
Do not re-expose patient to heparin ever again

warfarin effect

Warfarin poo poos on clotting factors 2, 7, 9, 10

which is more common immune thromboyctopenic purpua (ITP) or thrombotic thrombocytopenic purpura (TTP)

ITP

immune thromboyctopenic purpua (ITP) causes

Reduced platelet production in bone marrow

Excess destruction of platelet cells

Enlarged spleen
– Spleen is where autoantibodies are made
– Spleen is where platelets are phagocytosed

immune thromboyctopenic purpua (ITP) pathophysiology

Antibodies form against platelets → Autoimmune platelet destruction → Thrombocytopenia Muco-cutaneous bleeding

immune thromboyctopenic purpua (ITP) types - age - chronic/ acute - assocaited disorders - gender

Primary - in children (2-6y) - acute Secondary - in adults - Women - Associated with other autoimmune disorders, CLL, viral infections and tumours - chronic

immune thromboyctopenic purpua (ITP) presentation

``` Purpura -- Rapid onset Easy bruising Epistaxis (nose bleed) Menorrhagia Major haemorrhage rare May have history of viral infection /immunisation ```

immune thromboyctopenic purpua (ITP) investigations

FBC = isolated thrombocytopenia Platelet autoantibodies Bone marrow biopsy

immune thromboyctopenic purpua (ITP) management

- First line = corticosteroids (prednisolone) - Immunoglobulin given - to raise platelet count - Second line = splenectomy - If this fails, immunosuppression

thrombotic thrombocytopenic purpura (TTP) causes

Defiecincy of ADAMTS 13 (ADAMTS 13 is a protease that degrades vWF) - Congenital (absence of ADAMTS 13) - Autoantibody mediated (against ADAMTS 13) - Cancer - Drug associated - Pregnancy - Idiopathic

thrombotic thrombocytopenic purpura (TTP) pathophysiology

Deficiency of ADAMTS 13 (due to genetic abscence or autoantibodies). ADAMTS 13 is a protease that degrades vWF → widespread adhesion and aggregation of platelets → microvascular thrombosis → profound thrombocytopenia

thrombotic thrombocytopenic purpura (TTP) presentation

``` Florid purpura Fever Fluctuating cerebral dysfunction Hemolytic anaemia Renal failure ```

thrombotic thrombocytopenic purpura (TTP) investigations

- FBC - low platelets - Raised lactact dehydriogenase (from ischaemic/necrotic cells - as a result of haemolysis) - Coagulation screen normal

thrombotic thrombocytopenic purpura (TTP) management

- Plasma exchange - remove autoantibodies to ADAMTS13 - Corticosteroids (methylprednisolone) - Rituximab (monoclonal antibody) - Last resort = splenectomy

what could cause reduced platelet function (but normal numbers

- Congenital abnormality - Medication eg Aspirin - Von willebrand disease -- reduced vwF so platelets are unable to bind to damaged blood vessels resulting in platelet dysfunction (muco-cutaneous bleeding results) - Uraemia

hypersplenism effect on platelets

thrombocytopenia | portal HTN can cause - increased blood flow

liver damage effect on platelets

thrombocytopenia as liver produces TPO which stimulates platelet production and less TPO is produced in liver damage also: liver damage --> cirrhosis --> portal HTN --> splenomegaly --> thrombocytopenia

what could decrease production of platelets

Congenital thrombocytopenia - due to reduced/ malfunctioning megakaryocytes Infiltration of bone marrow - leukaemia, metastatic malignancy, lymphoma, myeloma Reduced platelet production - Low B12/ folate - Reduced TPO eg liver disease - Medication eg chemotherapy - Toxins eg alcohol - Infection eg HIV, TB - Aplastic anaemia = autoimmune

what could increase destruction of platelets

Autoimmune - ITP Hypersplenism - portal hypertension and splenomegaly Drug related immune destruction - eg heparin Consumption of platelets - DIC - TTP - in these cases their is activation of coagulation (via thrombin with DIC and lack of ADAMTS 13 with TTP) causing coagulation and platelet consumption so there are then fewer platelets (two steps!)