Haematinics, coagulation studies Flashcards
Iron studies for Iron deficiency anemia: sFe: sTIBC: sFerratin: Transferrin saturation: sTfR:
sFe: Dec sTIBC: inc sFerratin: Dec Transferrin saturation: dec sTfR: Inc
Iron studies for Anaemia of chronic disease: sFe: sTIBC: sFerratin: Transferrin saturation: sTfR:
sFe: N or dec sTIBC: dec sFerratin: N or inc (APR) Transferrin saturation: dec sTfR: N
What is the most common cause of congenital bleeding?
Name FIVE other congenital causes of bleeding.
VWD Haemophilia A & B Factor XI deficiency Collagen vascular disorders (Ehlers Danlos Syndrome) Platelet function disorders Hypo/dysfibrinogenamia
What is the most common acquired cause of bleeding?
Name FIVE other acquired causes of bleeding.
Medications Liver or renal disease ITP (immune thrombocytopenic purpura) BM disorders Cushing's syndrome Coagulation factors deficiencies (factor VIII, vWfactor)
Name FIVE key investigations for bleeding:
FBE (including differential & film) PT/INR & APTT Thrombin time Fibrinogen LFT & CrCl Ferratin
Name FIVE key investigations for bleeding:
FBE (including differential & film) PT/INR & APTT Thrombin time Fibrinogen LFT & CrCl Ferritin
What factors are involved in the EXTRINSIC coagulation pathway?
7 & tissue factor
What factors are involved in the COMMON coagulation pathway?
10, 5, 2, 1
What pathway(s) are tested via the INR? What drug is managed via INR
Common & Extrinsic
Warfarin
What pathway(s) are tested via the PT
Extrinsic
What pathway(s) are tested via the APTT
Common & Intrinsic
What is RDW?
What is the significance of an increased RDW?
Red cell distribution width = variation in size of the RBCs.
Increased ‘width’ reflects anisocytosis (not the same size RBCs) - meaning cells are in different states of maturity and of size.
Could be a mixed MICRO & MACRO cytic anaemia: where there are TWO RBC populations.
In MICROCYTIC anaemia, describe: Hb MCV PCV RDW WCC Plts Reticulocytes
Hb - low MCV - low PCV - N RDW - N WCC - N Plts - N Reticulocytes - N
Name FOUR common causes of MICROcytic anaemia:
Iron deficiency
Haemoglobinopathies (thalassemia)
Sideroblastic anaemia
Chronic disease
Name FOUR common causes of NORMOcytic anaemia:
Bleeding - acute
Haemolytic anaemia
Chronic disease
BM infiltration
Name SIX common causes of MACROcytic anaemia:
B12 deficiency (pernicious anaemia) Folate deficiency Alcoholism Aplastic anaemia Hypothyroidism Multiple myeloma BM proliferation
Describe the order in which FBE is reviewed when making a Dx about anaemia:
- Hb [low Hb = anaemia]
- Check ALL cell types:
2a. If only RBCs - an anaemia
2b. If all cells (R&W&P) - BM issue - Reticulocytes [raised during bleeding or haemolysis when immature RBCs are in the film
- MCV [micro, normo, macro]
- RDW [to ensure a single population of RBCs]
For each nutrient deficiency, name the type of anaemia:
Iron
Folate
B12
Iron - microcytic
Folate - macrocytic
B12 - macrocytic
Where is each nutrient absorbed?
Iron
Folate
B12
Iron - Duodenum & jejunum
B12 - Terminal ileum
Folate - Small intestine
What substance is required to assist with the absorption of B12?
What cells in what organ produce this substance?
What disease most commonly causes B12 deficiency?
Intrinsic factor
Parietal cells of the stomach
Pernicious anaemia
What is the most common deficiency causing anaemia?
What condition is this typically associated with?
Iron deficiency
Bleeding (menstrual or GI)
Regarding iron, what is?
Ferritin
Transferrin
Ferritin is the iron storage molecule
Transferrin is the transport molecule that moves Fe from blood to BM
In what substances is iron stored?
Hb
Ferritin
Heamosiderin
Which substance measured in haematinics is also an acute phase reactant that is increased by inflammation - such as that in chronic disease?
Ferritin
In anaemia of chronic disease, what would you expect Ferritin levels to be?
N or raised (because of its role as an acute phase reactant.
What THREE substances/tests can be measured/tested to reflect a state of active inflammation?
ESR
CRP (C-reactive protein)
Ferritin
Describe pernicious anaemia
autoimmune
defective intrinsic factor production
associated with antibodies against gastric parietal cells and intrinsic factor
What test is used to distinguish between causes of pernicious anaemia?
Apart from pernicious anaemia, what other conditions cause B12 deficiency
Schilling test
Bacterial overgrowth
What test detects folate deficiency?
serum folate levels
What tests show haemolysis (haemolytic anaemia)?
Hb (low)
BR - bilirubin (high)
BR is conjugated in the liver
(cBR) & converted to urobilinogen in the bowel & excreted in urine.
uBR in plasma will rise
UroBil in urine will rise
LDH (lactate dehydrogenase) rises when cell lysis occurs - LDH will rise too
What is a HAPTOGLOBIN?
Haptoglobins bind with Hb released from lysed RBCs and tpt it to the liver
During bleeding, haptoglobins can become saturated resulting in what substances being excreted in urine?
What substance can be found in the blood?
Hb - haemoglobinuria
Haemosiderinuria
Methaemalbumin(aemia)
What test detects methaemalbumin?
Schumm test
What test(s) detect autoimmune haemolysis [haemolytic anaemia]
Coomb’s test(s)
DAT = direct antiglobulin test
Indirect test
Compare the DAT and indirect Coomb’s test.
DAT tests for antibodies on the RBC surface
Indirect tests for antibodies in the plasma
What are the TWO main types of haemolytic anaemia?
Congenital (inherited)
Acquired
Name the THREE Inherited haemolytic anaemia mechanisms.
For each, name TWO relevant conditions.
- Abnormal RBC membrane:
1a. spherocytes
1b. elliptocytes - Abnormal Hb:
2a. Thalassemia
2b. Sickle cell anaemia - Abnormal RBC metabolism:
3a. Pyruvate kinase
3b. Glucose 6 PO4 dehydrogenase deficiency
Name the TWO types of acquired haemolytic anaemia:
Immune
Non-immune
Name FIVE immune acquired haemolytic anaemias:
AI warm AI cold Transfusion reaction HDN Adverse drug event
Name SIX non-immune acquired haemolytic anaemias:
malaria microangiopathic anaemia hypersplenism mechanical heart valve paroxysmal nocturnal haemoglobinuria burns
What is polycythaemia?
It can be apparent or true.
What causes ‘apparent’
Too many RBCs
Dehydration or stress erythrocytosis
What other name is given to primary polycythaemia?
polycythaemia rubra vera
Secondary polycythaemia arises from what TWO mechanisms?
Hypoxia
Excess EPO
What FOUR situations/conditions cause the hypoxia that gives rise to secondary polycythaemia?
lung disease
smoking
high altitude
cyanotic cardiac disease
What FIVE situations/conditions cause the excess EPO that gives rise to secondary polycythaemia?
adrenal tumour hepatocellular carcinoma cerebellar haemangioblastoma renal cell carcinoma polycystic kidneys
Name SEVEN common causes of neutrophilia (high neutrophils)
Bacterial infection Inflammation Necrosis (eg, post AMI) Steroid Rx Malignancy Metabolic disorders (RF) Myeloproliferative disorders
Name FIVE common causes of neutropenia (low neutrophils)
Chemotherapy
Radiotherapy
Adverse drug reaction (clozapine, carbimazole)
Viral infection
Felty syndrome [RA, splenomegaly & neutropenia]
Name FOUR common causes of lymphocytosis.
Viral infection
Chronic infections (TB)
Chronic Lymphocytic Leukaemia (CLL)
Lymphomas
Name SIX common causes of eosinophilia
Allergic disorders Parasite infection Skin diseases (Eczema) Malignancy (Hodgkin's) Allergic bronchopulmonary aspergillosis Hypereosinophilic syndrome
Name THREE causes of primary thrombocytosis.
Myelodysplasia
Chronic myeloid leukaemia (CML)
Essential thrombocythaemia
Name SIX causes of secondary thrombocytosis.
Infection Inflammation Malignancy Bleeding Pregnancy Post-splenectomy
Name the TWO mechanisms for thrombocytopenia:
Increased destruction
Decreased production - BM failure
Name EIGHT causes of BM failure causing thrombocytopenia.
Infection (esp viral - mononucleosis) Drugs (eg penicillamine) Leukaemia Aplastic anaemia Myelofibrosis BM replacment with tumour (myeloma or metastases) Myelodysplasia Megaloblastic anaemia
Name SEVEN situations where platelet destruction may occur:
After massive transfusion
DIC (diffuse intravascular coagulopathy)
TTP (thrombotic thrombocytopenic purpura)
HUS (haemolytic uremic syndrome)
Hypersplenism
Immune mediated: AITP (autoimmune thrombocytopenic purpura)
HIT (heparin induced thrombocytopenia)
What test should be done when a low platelet count is thought to be due to clumping?
Citrate test
Use a coagulation (blue) tube
Request ‘DO NOT SPIN’
so that the platelets can be counted
What is pancytopenia?
LOW levels of RBC, WBC & Plts
Name SIX common causes of pancytopenia:
Aplastic anaemia BM infiltration (by a tumour) Hypersplenism Megaloblastic anaemia Sepsis SLE (systemic lupus erythromatosis)
What is ESR?
What does it measure?
How does ESR change with age?
What is ESR a marker for?
Erythrocyte sedimentation rate
How rapidly RBCs sediment in 1 hour
ESR increases with age
ESR is a non-specific marker for inflammation
Name FIVE common causes of raised ESR
Infectious disease Neoplasia (esp MM) CT disease (esp GCA & PMR) Anaemia Renal disease
What condition is characterised by Auer rods in the WBCs
AML - acute myeloid leukaemia
What clotting factor is NOT reflected in APTT?
What drug is monitored using APTT?
VII
Heparin
What drug is monitored using INR?
What else is the INR an indication of?
Warfarin
Liver protein synthesis/function
What clotting factors are measured in PT?
Common [10, 5, 2, 1] &
Extrinsic [7]
What is DIC? (name & pathophys)
Disseminated Intravascular Coagulopathy
Both clotting & bleeding occur concurrently
What are the typical findings in DIC?
PT & APTT raised (clotting factors are reduced) Fibrinogen low (fibrin clots are forming) D-dimer raised (body attempting to break down excess fibrin deposits)
What does the D-dimer test measure?
Fibrinogen/fibrin degeneration as the body attempts to break down clots formed in the vasculature.
When is a negative D-dimer test useful?
To exclude PE or DVT
Consider PT, APTT & fibrinogen in DIC. What would each be respectively?
PT - increased (bleeding)
APTT - increased (bleeding)
Fibrinogen - reduced (clotting)
Consider PT, APTT & fibrinogen in LIVER DISEASE. What would each be respectively?
PT - increased (making fewer clotting factors)
APTT - increased (making fewer clotting factors)
Fibrinogen - normal (not clotting)
Consider PT, APTT & fibrinogen in WARFARIN treatment. What would each be respectively?
PT - increased
APTT - normal (or increased)
Fibrinogen - normal
Consider PT, APTT & fibrinogen in HEPARIN treatment. What would each be respectively?
PT - normal (or increased)
APTT - increased
Fibrinogen - normal
Consider PT, APTT & fibrinogen in HAEMOPHILIA A or B. What would each be respectively?
PT - normal
APTT - increased
Fibrinogen - normal
What happens in plasma cell dyscrasias?
What is the most common plasma cell dyscrasia?
What is the most important plasma cell dyscrasia?
M protein is produced in excess
MGUS - monoclonal gammopathy of unknown significance is most common
Multiple myeloma is most significant