Haematology Flashcards
What are the parameters and general causes of anaemia
<13.5 g/dl Men
<11.5 g/dl Women
Increased loss of RBC, reduced production, volume expansion (eg pregnancy)
What are the signs and symptoms of anaemia?
Signs- Conjunctival pallor
Symptoms- fatigue, fainting, SOB, headaches, palpitations, anorexia tinnitus
Severe- hyperdynamic circulation- tachy flow murmur (ejection systolic at the apex), HF
What are the causes of low MCV anaemia?
Normal RBC count with decreased actual content. F- Iron deficiency A- anaemia of chronic disease S- sideroblastic T- Thalassaemia
What are the causes of normocytic anaemia?
Anaemia of chronic disease Pregnancy Acute blood loss Bone marrow failure Hypothyroidism Renal Failure
What are the causes of macrocytic anaemia?
FAT RBC + Pregnancy Antifolates Hypothyroidism Reticulocysosis B12 deficiency + Folate Cirrhosis Myelodysplasia
Describe a blood film for iron deficiency anaemia
Microcytic, hypochromic, Poikilocytes, anisocytosis
What are the signs and symptoms specific to iron deficiency anaemia?
Brittle hair and nails, angular cheilosis. atrophic glossitis, koilinichynia
Post cricoid webs (plumbers Vinson -> dysphagia)
What are the causes of iron deficiency anaemia?
Blood loss - GI bleed ( peptic/ duodenal ulcers, NSAIDs, Ca, Crohn’s), menorrhagia, polyps, hookworm
Decreased intake - vegan/ vegetarian, poor diet, early life.
Increased usage- pregnancy, breastfeeding, infants
Poor absorptions - IBD, coeliac, tropical spruce, gastric band.
Intravascular haemorrhage- MAHA, PNH
What are the side effects associated with the treatment of iron deficiency anaemia?
Oral tables- abdominal discomfort, blood stool, constipation, nausea and diahorrea.
IV- high risk of anaphylaxis - therefore should not be used in sepsis.
Whata re the common causes of anaemia of chronic disease?
Renal failure Rheumatoid arthritis Vasculitis HIV, TB, Hepatitis, osetomyletis Malignancy
What is the pathophysiology of anaemia of chronic disease?
- In renal failure, increased INF, IL1 and TNF circulating due to chronic inflammation, leads to downregulation of the EPO receptor and inturn decreased EPO synthesis.
- IL6 and LPS increase hepcidin, which decreases iron absorbance, this causes increased sequestration of iron into macrophages -> deprives bacteria of iron
What is the cause of sideroblastic anaemia?
Ineffective erythropoesis -> iron loading -> haemosiderosis in heart, endocrine, liver
Lead toxicity, myelodysplasia, alcohol toxicity, cytotoxic drugs, post radio RIPE, myeloproliferative.
What are the blood film findings in sideroblastic anaemia?
Ring sideroblasts - erythroid precursors with iron deposits around the nucleus and mitochondria.
What is the treatment of sideroblastic anaemia?
Treat the cause +paroxidine
Why should you always check CRP with iron studies?
Ferritin is an acute-phase protein so may be altered in acute inflammation.
What are the iron studies for
a. Iron deficiency
b. anaemia of chronic disease
c. pregnancy
d. sideroblastic
Fe2+ TIBC Ferritin
a. v ^ v
b. v v ^
c. ^ ^ N
d. ^ N ^
What are the investigations for pancytopenia?
Abdo exam - spleen FBC - reticulocyte cound Iron studies, B12, Folate Blood film (Blasts, Hairy cell, dysplasia - leukaemia) Parvovirus PCR Myeloma screen Consider BM biopsy if nil else found
What are the megaloblastic and non-megaloblastic causes of macrocytic anaemia?
Megaloblastic
v B12, v Folate, Cytotoxic drugs
Non-megaloblastic
Alcohol excess, Pregnancy, Hypothyroidism, reticulocytosis
What are the findings on a megaloblastic blood film?
Megaloblasts- hypersegmented polymorphs, macrocytic anaemia, leucopenia, thrombocytopenia
What are the sources of B12 and Folate and therefore their respective risk factors for deficiency?
B12- Meat and dairy
RF- Vegan/ vegetarian, poor diet, tropical spruce, IBD, post gastric surgery, lactose intolerance, pernicious anaemia, SIBO, tapeworm
Folate - Leafy green vegetables, nuts, yeast
RF- Poor diet, IBD, tropical spruce, pregnancy, antifolates- trimethoprim, phenytoin, methotrexate, ^ cell turnover (CA, Haemolysis, inflammation, CKD)
What are the signs and symptoms of b12 deficiency anaemia?
Glossitis, angular cheilosis
Psych- irritability, depression, dementia, psychosis
Neuro- paraesthesia, peripheral neuropathy, areflexia, spastic paresis, subacute degeneration of the spinal cord
Define pernicious anaemia
and what is its treatment?
Autoimmune destruction of the parietal cells or intrinsic factor, leading to B12 deficiency.
Hydroxocobalamin IM
What are the investigations and findings in hereditary spherocytosis?
Blood film - spherocytes, membrane osmotic fragility
Coombs test: DAT -negative
Flow cytometry of RBC
What are the genetic inheritance patterns of which mutation for spherocytosis and elliptocytosis?
AD spectrin or ankyrin deficiency - hereditary spherocytosis
AR spectrin mutation:
South-East Asian ovalocytosis
Pyropoikilocytosis
AD spectrin mutations: All other elliptocytosis
What are the precipitants of a G6P deficiency attack?
Mothballs, acute infection, acute stress, broad beans (<1 day)
Medications: Asprin, primaquine, sulphonamides ( reaction 2-3 days)
What are the acute and diagnostic investigations for G6P deficiency?
Acute- Blood film - Bite cells, Heinz bodies (Blue deposits of oxidised haemoglobin), LFTs- Rapid jaundice -^ bilirubin. FBC- anaemia
Diagnostic- should be found on the Guthrie test. If not enzyme assay 3 months post-attack.
What is the presenting complaint of pyruvate kinase deficiency?
Severe and rapidly developing anaemia and jaundice at birth, splenomegaly
What is the pathology of sickle cell?
Single point mutation in the beta haemoglobin chain.GAG-> GTG, Glu -> Val at the 6th codon SCD - Hb SS Trait- Hb aS other rarer sickle cell phenotypes: Haemoglobin C disease Hb SC, Hb S Thal
What are the signs and symptoms in SCD of haemolysis and vaso-occlusion/ infarction?
Haemolysis: Anaemia, splenomegaly, folate v, gallstones, Aplastic crisis Vaso-oclusive/ infarction: Stroke Infections (hyposplenism and CKD) Crisis - splenic, painful& chest Kidneys- papillary necrosis and nephrosis Liver- gallstones Eyes- retinopathy Dactylitis (impaired growth) \+mesenteric ischaemia and priapism
When do the symptoms of SCD present (age split)
Childhood - stroke, splenomegaly and splenic crisis, dactylitis
Teenagers- priapism, stunted growth, gallstones depression
Adults- hyposplenism, retinopathy, CKD, Pulmonary HTN
What are the investigations for SCD?
Guthrie test Haemoglobin electrophoresis FBC- microcytic anaemia Blood film- sickle cells sickle solubility test.
What is the acute and chronic management of SCD?
Acute: Opioid pain management, Exchange transfusion, + additional if <60g/L Hb
Chronic
Folate and B12
Prophylaxis- ABX - pen, RSV, vaccinations - including flu
Regular exchange transfusions (check for need using carotid doppler monitoring)
Crixonlizumab (anti P selectin)
Allosteric stem cell transplant - curative
What are the signs, symptoms and radiological findings of beta thalassaemia?
Hepatosplenomegaly
XR- skull bossing, maxillary hypertrophy, hair on end skull
What is the spectrum of disease in alpha thalassaemia?
Hydrops fetalis a 4x0
a thal - a0x3 a1 moderate anaemia and splenomegaly
trait -moderate a01a1a+ a1/0
What is the purpose of the DAT (Coombs test)?
Detects Immune-mediated haemolytic anaemia
What are the different types of bleeding disorders and their clinical signs?
Vascular abnormalities
- easy bruising, nose bleeds & mucus membranes, immediate bleeding post-injury
Coagulopathy
- Delayed but profound and prolongedbleeding disproportionate to injury, bleeding into deep tissue eg muscle & joints
What are the congenital and acquired vascular defects that cause clotting issues?
Congenital: Osler-weber-rendu syndrome, connective tissue disorders (eg Ehlers Danlos syndrome)
Acquired: Senile purpura, steroids, scurvy-
Scurvy presentation: perifollicular hemorrhages- around hair follicle on legs due to ^ pressure in capillaries, infection - (meningitis, measles, degue)
What are the causes of platelet disorders?
Dysfunction
- Acquired: aspirin, cardiac bypass, uremia
-Congenital: Storage pool disease, thrombasthenia (glycoprotein v)
Thrombocytopenia
-v production -bone marrow failure
-^ destruction: (AITP=ITP), drugs- heparin, DIC, HUS, TTP
What are the differences between acute and chronic Idiopathic thrombocytopenic purpura?
Acute Chronic Age 2-6y/o adults F:M 1:1 3:1 pre-infection / rare Onset sudden abrupt-indolent Plt count <20k <50k duration 2-6 wks longterm remission spont uncommon - IVIg, steroids, splenectomy
When would you not give folate in the treatment of anaemia and why?
If you were not able to definitively rule out b12 deficiency as folate can exacerbate the neuropathies
Define haemolytic anaemia
Breakdown of RBC <120 days causing anaemia
What are erythroid hyperplasia states susceptible to?
Parvovirus - aplastic crisis
What do the blood tests for HA find generally?
^Bilirubin- unconjugated ^urogilogen ^LDH ^haptoglobin Methaemalbuminaemia Blood film: Reticulocytosis, ^MCV, Free Hb Hemoglobinuria
What are the heritable causes of HA?
Haemoglobinopathies -SCD -Thalassaemia Enzyme deficiencies -G6Pv -Pyruvate kinase v Membrane abnormalities -Spherocytosis -Elliptocytosis
What are the acquired causes of HA
Immune - ABO reaction -Warm/ cold AI Mechanical -metal valves, trauma, drugs, MAHA, PNH, infection eg malaria
What is the pathology of hereditary spherocytosis and elliptocytosis?
Spherocytosis - AD spectrin or ankyrin deficiency
Elliptocytosis - All are AD spectrin mutations except Southeast Asian and ovalocytosis which are AR
What are the differences between warm and cold AI HA?
Warm Temp: >37, IgG, spherocytes Both can be idiopathic or lymphoma Causes: CLL, SLE, methyldopa. Treatment: Steroids, splenectomy, immunosuppressants
Cold:
<37 IgM, Raynauds
EBV, TB
Treatment: cold avoidance or cause
What are the causes of paroxysmal cold haemoglobinuria?
Infection: EBV, Measles, VZV, syphilis
Donath-Landsteiner Antibodies bind to RBC but dissociate in warmth, these cause complement-mediated haemolysis on rewarming.
Is self-limiting as IgG dissociates at warmer temperatures
Explain the pathology of B thalassaemia
B0- no expression B+ - some expression B1 - normal
Minor: B+, B+ or B0B+ asymptomatic/ mild
Intermediate - B+/B1 or B0/B+ moderate anaemia - splenomegaly, bone deformities, gallstones
Major B0 B0 - Severe anaemia at 3-6mnths, FTT, hepatosplenomegaly, bone deformity, HF
What is the pathology of paroxysmal nocturnal haemoglobinuria?
Acquired loss of GPI markers (which have a protective function on RBCs, Plts and neutrophils)
-> complement mediated lysis of RBCs-> chronic intravascular haemolysis at night
What are the investigations for paroxysmal nocturnal haemoglobinuria?
Morning -Urine dip haemoglobinuria
Coombs - DAT+
Immunophenotyping shows altered GPIs
(Ham’s test shows in vitro acid induce haemolysis)
Describe a blood film for MAHA and its pathology
Spherocytes- caused by RBCs getting damaged passing through fibrin - caused by HUS, TTP, eclampsia/ pre-eclampsia, DIC
What is the pathology of thrombotic thrombocytopenic purpura?
AI destruction of ADAMTS13 (this forms strands of VW factor that cuts through the RBCs)
What are the symptoms of TTP?
MAHA, Fever, renal impairment (worse in HUS), neurological abnormalities, thrombocytopenia
What is the pathology of haemolytic uraemic syndrome?
E.coli toxin destruction of endothelium -> fibrin mesh-> damaged RBC -> impaired eGFR +MAHA
What is the process of haemostasis from injury to stable plug (don’t include detail of clotting cascade)
Injury
- vasoconstriction -> decreased blood flow = stable plug
- platelet aggregation -> activates stable plug
- direct TF stimulation of clotting cascade
- crossing linking and fibrin stabilisation
Describe the clotting cascade
Extrinsic pathway
TF
7->7a
5->5a
Intrinsic 12->12a 11->11a 9->9a 8->8a 10->10a 5->5a Common 5->5a prothrombin ->Thrombin Fibrinogen -> fibrin Plasminogen --TPA(Tissue plasminogen activators)--> plasmin ^ fibrin degregation
What parts of the coagulation cascade to aPTT, Pt and TT look at and their function
aPTT- activated partial thromboplastin time - Intrinsic pathway monitoring heparin
PT- Prothrombin time (INR), -Extrinsic Warfarin (INR)
TT- Thrombin time common pathway - starts at 5a
Describe the pathology of Haemoophalia A and B
Both are X-linked recessive
A- Factor VIII deficiency, 1/10Kmales
B- Factor IX deficiency 1/50Kmales
Describe the investigations for haemophilia A
^aPTT, normal PT and TT, v FVIII on assay
What is the management of
a. haemophilia A
b. haemophilia B
c. VWD
a. Avoid NSAIDs, IM injections.
Give desmopressin (as it causes VWF release, which carries factor VIII), F VIII replacement -life long
b. F IX replacement
c. May need prophylaxis, but treatment for acute bleeds is VWF and F VIII replacement, desmopressin
Describe the aetiology of von Willebrand’s disease
Type 1: defcicency in VWF
Type 2: impaired function of VWF
Type 3: Absent VWF (can present as haemophilia A)
All will have v plt function and v FVIII (as VWF carries F VIII)
AD- 1/10K
How does VW disease present + investigation findings?
Mainly as a platelet issue (mucosal, easy bruising), but can present as a clotting factor issue (deep bleeding)
^/-aPTT, normal PT, vF VIII, vVWF antigen (normal in T2), -plts
What is the cause of DIC?
Widespread activation of the coagulation leading to consumption of clotting factors and platelets
instigated by
- malignancy, sepsis, trauma, obstetric complications, toxins
What clotting functions are affected in liver disease?
v synthesis of II, V, VII, VIII,IX, XI
v Vitamin K absorption
abnormal platelet function
What are the bleeding risks associated with warfarin and why?
Warfarin is a vitamin K antagonist meaning there will be decreased F II, VII, IX and X.
It can also decrease protein S and C so may initially have a procoagulant effect but will ultimately be anticoagulant.
What can cause vitamin K deficiency and how can you treat it
Warfarin, vit K malabsorption/ malnutrition, Abx, biliary obstruction.
Treat with IV vit K or FFP in acute haemorrhage
What are the investigation findings in DIC?
Plts v, v fibrinogen, ^D-dimer, ^PT
Name 5 neonate specific causes of anaemia
Birth trauma Twin to twin transfusion (one ends up anaemic and one polycythaemic) Foetal to maternal transfusion Parvovirus haemorrhage from the cord or placenta
What is congenital leukaemia
transient abnormal myelopoiesis
Associated with Downs
It can pass between twins
Define a thalsaemia and haemoglobinopathy
Thalassaemia is a reduced synthesis of one or more globin chains due to a genetic defect
Haemoglobinopathy - synthesis of structurally abnormal molecule
Which globin chains are on Chr11?
Beta Delta Gamma Locus control region for all these chains Epsilon - embryonic
Which globin chains are on Chr16?
Alpha
Zeta