Haematology Flashcards
Indications for thrombophilia screening
DVT < 45
Unexplained recurrent venous thromboses @ unusual site
Recurrent miscarriage
Arterial and venous thrombosis
Risk factors for arterial thrombosis
Smoking, HTN, Atherosclerosis, Hyperlipidaemia, DM, ? APS, F V leiden, MTHFR
Factor V leiden relative risk for VTE
5-7 x for heterozygotes, 80x for homozygotes, 35 x if using OCP
FVL + prothrombin gene mutation together account for 5-6-% inherited procoagulable states, FVL is the most common
Antiphospholipid antobodies
Lupus anticoagulant
Anti cardiolipin
beta glycoprotein- 1
can’t check lupus anticoagulant when anticoagulated
Anti thrombin III deficiency
can be heparin resistant, can be found spuriously low in acute thrombosis or illness, heparin can lower ATIII levels by up to 30%
8x higher lifetime risk of VTE
Protein C + s deficiency
7/8 x higher lifetime risk of VTE
measurement protein c + S only after 2 weeks OFF anticoagulation
warfarin can cause skin necrosis in protein C deficiency
Polycythaemia Rubra Vera
95-97% JAK 2 +ve
Plethora, conjunctival injection, fundal hyperviscosity, pruritic after a warm bath, GOUT
2% incidence of AML, usually eventual myelofibrosis.
Essential thrombocytosis
50% JAK2+ve
thrombosis, bleeding, splenomegaly
Rx depends on symptoms; ? aspirin, hydroxyurea
CML
Philadelphia chromosome 9;22 BCR-ABL
fatigue, anaemia, pancytopenia, B symptoms, bone pain, Splenomegaly +++ -> blast crisis => 20% blasts
Imatininib has revolutionised Mx -> molecular remission, monitored on PB Bcr-ABL
Myelofibrosis
40-60% JAK2+ve Leukoerythroblastic anaemia
Splenomegaly
poor prognosis if Hb < 100, WCC < 4 or > 30 constitutional Sx
5-10% transform to AML
Anaemia in renal disease
decreased EPO, BM suppression from uraemia + decreased blood cell survival, uraemia platelet dysfunction leads to increased RBC loss, blood loss in dialysis, BM suppression from aluminium, Osteitis fibrosa from hyperparathyroidism
anaemia in hypopituitarism
anaemia (normochromic / normocytic) also usually leukopenic; reverses with hormone replacement
Causes of thrombocytopaenia
Normal 150 - 450, usually no issues if > 100, risk of spontaneous haemorrhage < 20
Hypersplenism ->causes sequestration
Dilutional loss (Transfusion)
BM failure, BM infiltration (Leukaemia, Lymphoma , Myeloma, MDS, Myelofibrosis, Metastatic carcinoma, Marrow suppression -> drugs / chemo / RT, Nutritional deficiency -> b12/folate, Hereditary causes -> Fanconi, congenital megakaryocytic hypoplasia
Increased destruction -> Immune (ITP, drug induce thrombocytopaenia, HITS, Arc with SLE, LPD, infection (HIV, other viruses, malaria, post transfusion purpura
Non immune - TTP / HUS, DIC, bypass surgery, congenital acquired heart disease
antiphospholipid syndrome
1st trimester preg loss
can be associated with SLE or other conn tiss diseases
Prolonged APTT that does not correct with mixing studies
Catastrophic -widespread thomboses with multi organ failure, may have DIC like profile
3 or more organ / systems involved, all develop within one week , histopath confirms small vv occlusion of at least once organ, lab assay confirming APLS Abx
Ix: Anticardiolipin IgG and IgM (less specific) + lupus anticoagulant (Cannot be tsted when anti coagulated), B2GP-1.
Arterial event - > lifelong anticoagulation, LMWH + aspirin in prep if recurrent miss. catastrophic -> anticoagulant + steroids
Haemolytic anaemia causes
Hereditary - RBC memb defects and enzymopathies, abnormal Hb -> that, sickle
any extramedulary haematopoesis?
Acquired immune - >transfusion incompatibility, haemolytic disease of the newborn
Autoimmune - > warm AIHA - primary or secondary to CLL , SLE, drugs
Cold -> EBV, mycoplasma, cold agglutinin disease, lymphoproliferative disorders, PNH.
Acquired non immune - infections (viral , malaria, babesiosis, clostridium perfringens), microangiopathic (TTP, HIS, HELP, DIC), Mechanical (valve disease/ prosthesis), chemical (Oxidative haemolytic, lead poisoning, hyperbaric O2), Physical damage (burns, liver disease, march haemolysis, bongo drum playing)
Define recurrent infections for investigation of immunodeficiency
2 major OR 1 major and recurrent minor infections in 1 year, unusual orgs (Aspergillus/ pneumocystis), unusual sites -> liver abscess, osteomyelitis, chronic infections-> sinusitis cellulitis, structural damage -> eg bronchiectasis
Immune system interrogation for immune def
EXCLUDE HIV!!
B cell - IGs + subclasses
serum + urine EPG / IEPG, response to immunisations, flow cytometry
T cell function - Flow cytometry to check absolute counts
Neutrophil function - neut count, blood film
Complement assays
Exclude secondary causes - renal disease, bowel disease (loss of Ig and lymph), malignancy, nutritional deficiency, drugs (esp cytotoxins, anticonvulsants)
Lymphadenopathy - also CT sinuses, CXR, CT chest , PFTs
Classification of immunodeficiency
Genetic - AR, AD, X linker, gene deletions
biochemical + metabolic def
Vitamin / mineral - zn, B12, biotin
Undefined primary - CVID, Specific antibody def, IgG subclass def, IgA def
Maturational - transient hypo gamma of infancy
Secondary - viral , HIV, CMV, EBV, rubella
Chronic infection TB
malignancy (Lymohoma leukaemia), splenectomy, extremes of age, transfusion Rx, drugs, plasmapheresis, radiation, nutrition, chronic renal disease (incl, dialysis), toxins (ETOH, cigs)
graft V host disease
higher incidence in unrelated
can also occur in severe imnuosuppression after Tx - rare
Acute GvHD before day 100 post SCT, Chronic > day 100
RFs - older recipient /donor
fever , rash, Abn LFTs, diarrhoea (+/- viral reactivation esp CMV)
Thrombocytpaenia BAD
Rx - steroids? Cyclosporine, Tac, Azaz, MMF, HCQ, *ALG) also supportive Rx (IVF, TPN)
Hodgkins lymphoma
B symptoms
Wloss > 10% in 6/12
bimodal distribution age 20-29 or > 60
3, 100,000
Reed sternerg cells (owls eyes)
ann arbor 1,11 above, iii Iv above and below.
Rx - ABVD chemotherapy (Doxorubicin, bleomycin, Vinblastine, Dacarbazine)
Haemophilia treatment
