haem middle tier Flashcards
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)
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
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
signs of polycythaemia
hepato/splenomegaly
abnormal FBC
hypertension
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
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)
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
polycythaemia complications
Acute myeloid leukaemia
Thrombotic events -clots etc
relative polycythaemia
Apparent polycytaemia
- Chronic
- Associated with obesity, hypertension, high intake of alcohol/ tobacco
Dehydration
- Acute
- Cause = dehydration eg alcohol , diuretics
primary causes of polycythaemia
- Mutations in EPO receptor
- High oxygen affinity haemoglobins
- polycythaemia vera
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
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
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
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
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
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!)
