Haematology theory Flashcards
Thrombotic thrombocytopenic purpura (TTP):
[ ? ] Clinical: FAT RN (pentad)
Ix: ADAMTS13 deficiency, less cleaving vWF = microthombi, end organ ischemia.
Mx: PLEX, high dose steroid.
Fever
Haemolytic Anaemia
Thrombocytopenia
Renal failure
Neurological abnormalities
Drugs causing warm ab immunohemolytic anaemia (WAIHA)
Methyldopa
Pencillin
Quinidine
Fludarabine (CLL, NHL) unless combined with rituximab (CD20)
Drugs to avoid in G6PD
G6PD: oxidative hemolysis -> heinz bodies / bite cells, X-chromosomes (males), fava beans.
Antimalarials
Sulfonamides
Co-trimoxazozle
Dapsone
Risk factors for hemolytic anaemias
1.FHx + ethnicity
- greek or italian
- china/south east asian
- african/mediterranean/asian
2.Warm antibody hemolytic anaemia (2)
3.Tertiary syphilis
4.Secondary:
-DIC
-HUS
4.Trauma:
-Mechanical heart valve
-Joggers
5. Organ dysfunction:
-splenomegaly
-cirrhosis
FHx + ethnicity
- greek or italian: beta-thalassemia trait
- china/south east asian: alpha-thal
- african/mediterranean/asian G6PD
Warm antibody hemolytic anaemia
- SLE and other CTD
- Lymphoma (warm and cold ab)
Tertiary syphilis (paroxysmal cold hemoglobinuria)
Secondary:
-DIC: malignancy, renal graft rejection, HTN
-HUS (gastroenteritis, e.coli 0157:H7 infection not for abx).
Trauma:
Mechanical heart valve (aortic > mitral) with paravalvular leak
Joggers (external trauma)
Organ dysfunction:
-splenomegaly
-cirrhosis (spurr cell anaemia)
Fever in hemolytic anaemia (4)
Septicemia
Malaria-associated hemolysis
Acute sick cell crisis
TTP
Hemolytic anaemia blood film (3)
Coombs test:
-warm ab
-cold ab
Blood film:
- schistocytes (valve hemolysis, DIC, TTP or HUS)
- polychromasia
- hypochromic and microcytic (thalassemia).
Coombs test (immunohemolytic):
-warm: lymphoma (NHL), CLL, solid tumours (lung, colon, kidney, ovary), SLE and drugs, idiopathic
-cold: EBV, mycoplasma, hepatitis C, lymphoma, idiopathic
-paroxysmal cold hemoglobinuria (rare)
Multiple myeloma
1. Investigation
-Myeloma specific (4)
-CRAB
-MRI
-Prognostication (2)
2. Treatment
-Prevent renal failure
-Bone marrow suppression
-Bone lesions
-Systemic tx
. if eligible for SCT
. if not eligible for SCT
-SCT
3. Complications
- INVESTIGATION.
-Myeloma specific:
. BM bx (clonal plasma cells >10% or plasmacytoma)
. SPEP (monoclonal globulin peak)
. Serum/urine paraprotein (IgG > IgA > IgM)
. Serum/urine light chains (bence-jones proteinuria and kappa:lambda ratio)
-CRAB:
. Calcemia (bone pain, abdo pain, dehydration, infection)
. Renal disease: renal function and urate level
. Anaemia: FBC and ESR
. Bone lytic lesions: XR- skull, proximal long bones (also for fracture, osteoporosis)
-MRI ?spinal cord compression or nerve root.
-Prognostication:
. Serum B2 microglobulin
. Albumin - TREATMENT
-Indications
. >60% plasma cells
.serum free light chains >100
. MRI lesion >5mm
. hypercalcemia
. renal failure
. anaemia
. lytic lesions
-Prevent renal faliure:
. Hydration, bicarbonate
. Allopurinol for urate nephropathy
. Caution IV contrast
-Bone marrow suppression:
. Avoid live vaccines
. EPO for anaemia
-Bone lesions:
. Bisphosphonates (Zolendronic acid)
. RTX (local irradiation, symptomatic benefit)
-Systemic tx if symptomatic or end-organ damage:
. IF eligible for SCT = steroid +/- thalidomide or CYC OR bortezomib + dex + CYC
. IF not eligible for SCT = melphalan + prednisone + (thalidomide/bortezomib/lenalidomide)
. SCT
3. COMPLICATIONS
-peripheral neuropathy (bort/ thali)
-thrombosis (lenali)
-infection
. secondary hypogammaglobulinemia (IVIG)
-bone
. Lesions
. Bisphosphonate complications
-steroid
-psychogical
-“geriatric” (frail)
DDx multiple myeloma (4)
MGUS
-serum paraprotein <30g/L
-bone marrow plasma cell infiltrate <10%
Smouldering multiple myeloma
-serum paraprotein >30g/L
-bine marrow plasmacytosis >10%
-absence of crab features
Waldenstroms macroglobulinemia
-monoclonal IgM peak EPG
-hyperviscosity
-similar symptoms
-Tx: plasmapharesis, prednisone, fludarabin
POEMS syndrome: osteosclerotic myeloma
-polyneuropathy
-organomegaly
-endocrinopathy
-monoclonal gammopathy
-skin changes
Complications autologous SCT: high dose chemo
D5-10: pancytopenic
D14: neutrophil
Organ toxicity (renal, VTE)
Infection:
-peritransplant (febrile neutropenia)
-late: HSV/VZV, PJP, CMV
-prevention
. Immunoglobulin
. Prophylaxis
. Vaccination
. Minimise immunosuppression (steroids)
Allogeneic transplant
Complications
-GVHD prophylaxis
-Pancytopenia
-VTE
-Mucositis
-CMV/EBV
Complications-
-GVHD prophylaxis (cyclosporin)
. Acute: skin, liver, GIT. Tx: high dose steroid, calcineurin inhibitor, MYC, ruxolitinib (JAKi). C/o- fungal, CMV, opportunistic.
. Chronic: D100+ scleroderma, as above + functional hyposplenism
-Pancytopenic
-VTE
-Mucositis (TPN/PCA)
-CMV / EBV reactivation: monitor viral load, tx: wean immunosupp, gan/valganciclovir (myelosupp), foscarnet.
CHA2DS2VASc
>1 mod
>2 high
CHF
HTN
Age >75
Diabetes
Stroke/TIA/VTE
Vascular disease
Age >65
Sex category (FEMALE)
HASBLED
>3 caution
HTN
Age >65
Stroke
Bleeding tendency or predisposition
Labile INR
Elevated renal / LFT
Drugs (blood thinners) or alcohol
Immune thrombocytopenia (ITP).
-autoimmune, anti-platelet IgG antibody
-clinical features
-investigation
-treatment
CLINICAL FEATURES.
-thrombocytopenia
-purpura
-haemorrhage
INVESTIGATIONS.
-platelet
-blood film
-bone marrow
-anti-platelet antibodies
-SLE (ANA, anti-dsDNA, complement)
TREATMENT.
-spontaneous improvement
-transfusion if acute bleeding + steroids
-if severe, IVIG
-splenectomy
Thrombocytopenias
A. Increased platelet destruction
B. Decreased platelet production
A. Increased platelet destruction.
-Immune thrombocytopenia
. idiopathic thrombocytopenic purpura
. secondary autoimmune thrombocytopenia
. drug-induced immune thrombocytopenia
. post-transfusion purpura
. viral infection (HIV)
-Consumptive thrombocytopenia
. TTP
. DIC
. HUS
-Hypersplenism (sequestration).
B. Decreased platelet production.
-bone marrow suppression (drugs, alcohol, toxins, infections)
-aplastic anaemia (pancytopenia)
-leukemias and bone marrow cancers
-megaloblastic anaemia (b12 defcieicnY)
Antiphospholipid syndrome
Abs (12 weeks):
1.anticardiolipin ab
2.lupus anticoagulant (prolong APTT)
3.anti-b2 glycoprotein
Features:
-thrombosis
-recurrent pregnancy loss
-haem: thrombocytopenia, haemolytic anaemia
-renal: acute thrombotic microangiopathy, chronic vaso-occlusive lesions
-cardiac: valve vegetation or thickening
-derm: livedo reticularis or racemosa, livedoid vasculopathy (recurrent painful skin ulcers)
-neuro: cognitive, subcortical white matter changes
Associated with SLE / Sjogrens.
Mx: LDA + LMWH in pregnancy, anticoagulation lifelong if VTE / infarct.
ITP v TTP v DIC
ITP - antiplatelet ab, steroid, IVIG, splenectomy
TTP- adamts13 deficiency, endothelial defect, plex (remove autoantibodies and large VWF), steroids
DIC- thrombin excess, increased d-dimer, increased INR, supportive.
Disseminated intravascular coagulation (DIC)
Pathophysiology:
tissue factor from vascular endothelial damage (trauma, chemo, bacteria, cytokine exposure)
activates factor VII -> extrinsic pathway coagulation cascade
thrombin and fibrin formed
clotting factors consumed -> excess bleeding
platelets trapped and consumed.
clinical history: severe infection, trauma, hepatic failure, obstetric complications, maligjnancy
VTE
bleeding
renal failure
end-organ damage (lungs, pulmonary haemorrhage or embolism)
coronary artery disease
stroke
Mx: secondary cause, mx active bleeding with platelet/ FFP, if not actively bleeding VTEp with heparin / LMWH.
Microcytic anaemia
Thalassaemia
Iron deficiency: central pallor > 1/3
Anaemia of chronic disease
-hepcidin blocks ferroportin gate that lets iron into gut / macrophage.
Lead toxicity: basophilic stippling (polka dot)
Sideroblastic anaemia: ring sideroblasts.
1. Hereditary. Mx pyridoxine, blood tf for anaemia.
2. Acquired (drugs, chemo, MDS/MPN). Mx avoid agent, c/o diabetes.
Macrocytic anaemia
EtOH
Liver disease
Myelodisplastic syndrome (sideroblastic)
B12/folate def
Drugs (phenytoin, cytotoxics, anti-virals, trimethoprim)
Reticulocytosis (haemolytic anaemia, bleeding)
Myeloma
Haemochromatosis
Smoking
Others- aplastic anaemia, COPD, anorexia, hypothyroidism, familial, pregnancy.
Normocytic anaemia
Decreased production, less reticulocytes
-inflammation
-nutrient def
-EPO def
-bone marrow infiltration
-MDS
-chemo
Increased loss or destruction, more reticulocytes.
-acute bleed
-haemolysis
Autoimmune haemolytic anaemia
Anaemia
Reticulocytes
Bilirubin (unconjugated)
Low haptoglobin
Direct antiglobulin test (DAT)
Hereditary spherocytosis
Auto dominant
Red cell membrane protein abnormality
Splenic destruction
Pigment gallstones
Anaemia
Mx: splenectomy
Splenectomy
-blood film
-acquired hyposplenism
. infarction
. atrophy/hypofunction
. infiltration
Blood film:
Howell Jolly bodies
Target cells
Spherocytes
Odd cells
Acquired hyposplenism:
Infarction: sickle cell, ET, PRV
Atrophy/hypofunction: coeliac, dermatitis herpetiformis, IBD, autoimmune (RA, SLE, GN, PBC, Sjogrens, MCTD, thyroiditis), irradiation, BMT/GVHD, HIV/AIDS
Infiltration:
Amyloid
Sarcoid
Leukaemia
Myeloproliferation
Cold agglutinin disease (EBV, mycoplasma, lymphoma)
Cold agglutinin + haemolytic anaemia
- primary = distinct lymphoma
- secondary = infection, lymphoma
Haemolytic uraemic syndrome
E.coli producing shiga-toxin
Strep pneumoniae
Atypical HUS
P- bloody diarrhoea, severe crampy abdo pain, nausea, vomiting.
VWF secreted from toxin-stimulated kidney endothelium
Thrombotic microangiopathy
VWF deficiency
-genetic
-acquired
Acquired
-aortic stenosis
-LVAD
-ET (high plt)
-immune mediated
-malignancy
-hypothyroid
Heyde syndrome (3)
- aortic stenosis
- acquired von willebran syndrome
- GI bleeding
Heparin induced thrombocytopenia (HIT) 4T score
Thrombocytopenia
Timing of platelet count fall (d5-10)
Thrombosis or other sequelae (skin lesion, systemic reaction)
Other cause for thrombocytopenia (none)
PF4-heparin antibodies
Haemophilia A and B
X-chromosome (males)
Replacement
Prophylaxis 2-3x week
Haem A : F VIII (inhibitors developed, emicizumab bypass, immunosuppression = CYC, RTX, IVIG)
Haem B: F XI
Clotting cascade
Extrinsic pathway (PT) little
Intrinsic pathway (APTT) TENET
Vit K antagonist (warfarin) = factor 2, 7, 9, 10
Factor Xa inhibitors = rixaroxaban, apixaban, fondaparinux, LMWH (PT, modified anti-Xa assay)
Antithrombin = LMWH, UFH, dabigatran, bivalrudin (thrombin time, APTT)
Warfarin + bleeding
Other anticoagulation and surgery (planned / unplanned)
Vit K
Prothrombinex
FFP
Myeloproliferative neoplasm investigations
FBE: count and film
PCR/FISH: BCR-ABL1 for CML
PCR: JAK2, CALR, MPL
BM bx: hypercellular, fibrosis on reticulin stain
CLL indications for tx
anaemia or immune thrombocytopenia
painful lymphadenopathy
B-symptoms: fever, chill, weight loss
lymphocyte doubling time <6/12
rapidly enlarging lymph nodes or organs
autoimmune hemolytic anaemia or idiopathic thrombocytopenic purpura refractory to immunosupp
Acute myeloid leukaemia
Auer rods
Electrolytes, renal, liver, uric acid, LDH
Coagulation profiles
BM bx >20% blasts
Cytogenetics
Myelodysplastic syndrome
Allogeneic HSCT
Transfusion
-iron chelation
-plt
GCSF, EPO
Chemo - azacitadine
Lenalidomine (chr 5q31 deletion)
Acute intermittent porphyria
Auto dominant
Abnormal haem production
P: Abdo pain, neuropsych sx, peripheral neuropathy
R: triggered by alcohol, fasting, medication
D: Porphyrobilinogen, porphyrin in urine (days after attack).
M: IV haem c/o VTE risk. orthotopic liver transplant.
C: hepatic iron overload, liver fibrosis.
Anticoagulation
-Factor Xa inhibitors
-Direct thrombin inhibitor
Debate against warfarin.
Factor Xa inhibitors: rivaroxaban, apixaban
Direct thrombin inhibitor: dabigatran
DEBATE AGAINST WARFARIN:
Novel anticoagulants advantages: rapid onset of action, fewer interactions with meds/food, no need for repeat bloods.
Disadvantages: not safe in renal failure,
Haematology fundoscopy (2).
Choroid infiltration (chronic leukemia) or leopard skin.
Retinal gross venous dilatation and segmentation in hyperviscosity.
Hodgkin’s v non-Hodgkin’s lymphoma (HL v NHL)
B symptoms poorer prognosis.
Reed-sternberg cells in Hodgkin’s, binucleate cells on light microscopy of biopsy.
B-symptoms: weight loss (>10% 6 months), fever, night sweats.
Chronic lymphocytic leukemia (CLL)
-monoclonal proliferation (lymphocytes, B-cells).
-routine bloods with raised wcc
-bone marrow failure or constitutional symptoms
-Ix
-Binet system staging
-Mx
Ix:
-CT
-LN bx
-BM bx
-cytogenetics
Binet staging
-stage A <3 groups (watch and wait)
-stage B >3 groups
-stage C anaemia or thrombocytopenia
Mx:
-chemo: fludarabine and CYC
-monoclonal antibodies: rituximab
-Jaki: ibrutinib, idelalisib
-BM transplant
Complications:
-bone marrow failure
-autoimmune haemolytic anaemia
-recurrent chest infections
-acute transformation (richter’s syndrome) into aggressive lymphoma (DLBCL = fever, rapid node enlargement, severe LDH rise and high-grade NHL).
Myeloproliferative disorders
-RBC
-WBC
-Plt
-Fibroblasts
CML dx: bloods, cytogenetic tests (Chr 9- philadelphia chromosome, BCR-ABL1 gene targetted by tyrosine kinase inhibitors e.g. imatinib).
RBC: PRV
WBC: CML
Plt: Essential thrombocythemia
Fibroblasts: myelofibrosis
Purpuric / petechial rash
Febrile
1. palpable (infection / HSP)
-meningococcal
-disseminated gonococcal
-endocarditis
-henoch-schonlein purpura (IgA vasculitis, arthralgia large joints, nephritis, HTN).
- non-palpable
-purpura fulminans
-DIC
-TTP
Afebrile
1. palpable
-autoimmune vasculitis
- non-palpable
-immune thrombocytopenic purpura
