Blood Disorders Flashcards
What are the constituents of a red cell count?
Hb MCV Reticulocyte count Red cell count Haematocrit MCH
What is the reticulocyte count? What does it mean if its high?
The concentration of immature RBCs
High: increased blood loss and haemolytic anaemia because the bone marrow works harder to replace lost cells
What is the haematocrit?
Volume percentage of RBCs in the blood
What causes a microcytic anaemia?
Iron deficiency anaemia Thalassemia Sideroblastic anaemia (production of ringed abnormal RBCs)
What causes a normocytic anaemia?
Acute blood loss
Haemolytic anaemia
Chronic disease
Multiple myeloma
What causes a macrocytic anaemia?
B12/folate deficiency Alcohol Reticulocytosis Liver disease Pregnancy
What is a physiological cause of normocytic/macrocytic anaemia?
Pregnancy
What tests are included in a haematinics study?
B12/folate
Ferritin
What does a high/low ferritin tell us?
High - not useful as ferritin is an acute phase protein so rises with any inflammation
Low - iron deficiency
What causes iron deficiency anaemia? What are the signs?
- Chronic blood loss (menstrual/GI/urinary)
- Increased demand
- Decreased absorption (coeliacs - do tTg), gastrectomy)
- Poor intake
SIGNS - koilonychia, angular stomatitis, glossitis
How is iron deficiency anaemia treated?
Ferrous sulphate tablets
Transfusion if Hb<70
How is B12 absorbed?
Binds to intrinsic factor, allowing it to be observed in the terminal ileum
What causes B12 anaemia?
- Pernicious anaemia
- Malabsorption
- Not enough meat/fish etc
What causes folate deficiency anaemia?
- Increased requirements
- Dietary (not enough green veg)
- Malabsorption
- Drugs (trimethoprim, phenytoin)
What are some heritable causes of haemolytic anaemia?
Haemoglobinopathies: sickle cell
Membrane defects: hereditary spherocytosis, elliptocytosis
Enzyme defects: G6PD deficiency, pyruvate kinase deficiency
What are some acquired causes of haemolytic anaemia
Autoimmune (DAT+) - drug induced
Non-immune: DIC, TTP, infection
What is Coombs test for?
Autoimmune haemolytic anaemia - DAT direction antiglobulin test
What is polycythemia?
Increased number of RBCs in the blood
What are the primary and secondary causes of polycythemia?
Primary - polycythemia vera (all cell lines increased)
Secondary - increased epo or chronic hypoxia (just RBC increased)
What causes a high/low neutrophil count?
High - bacterial infection, inflammation, steroids, malignancy, stress
Low - chemo, agranulocytosis 4Cs (carbamazepine, clozapine, colchicine, carbimazole)
What causes a high/low lymphocyte count?
High - viral infection, CLL, chronic infections
Low - viral infection, HIV, chemo, bone marrow failure
What causes a high/low monocyte count?
High - bacterial infection, autoimmune disease, leaukemia
Low - acute infection, steroids, leukemia
What causes a high/low eosinophil count?
High - allergy, parasite, drug reactions
Low - n/a
What causes a high/low basophil count?
High - leukaemia, hypersensitivity, myeloproliferative disorders
Low - n/a
What causes thrombocytopenia?
Decreased production - bone marrow failure, megaloblastic anaemia
Increased destruction - DIC/TTP/ITP/SLE/CLL/viruses/drugs
What causes thrombocythemia?
Primary - myeloproliferative disorders
Secondary - bleeding, inflammation, infection, malignancy
What is a myeloproliferative disorder?
A group of neoplastic disorders involving the bone marrow cells that produce RBCs, platelets or fibroblasts (everything except WBCs)
- Essential thrombocythemia
- Chronic myeloid leukemia
- Polycythemia vera
- Myelofibrosis
What is essential thrombocythemia and how does it present?
Overproduction of platelets by bone marrow
- asymptomatic, headache, dizziness, bruising, thrombosis
What do investigations show for ET?
a) bloods
b) genetics
B: Isolated rise in platelets
G: JAK2, CALR or MPL mutation
How is ET treated?
- Aspirin to reduce clot risk
- Cytoreductive surgery
- Hydroxycarbamide
What is chronic myeloid leukemia and how does it present?
Neoplastic disease of mature myeloid cells in the bone marrow, involving basophils, eosinophils and neutrophils
- incidental finding, fever, night sweats, splenomegaly, weight loss, bleeding, petechia, gout, hyper-viscosity syndrome
3 clinical phases:
- Chronic
- Accelerated
- Blast crisis (symptoms of AML)
What do investigations show for CML?
a) bloods
b) cytogenetics (most important test)
a) increased myeloid cells, myeloblasts
b) translocation(9:22) involving the ABL:BCR genes - PHILADELPHIA CHROMOSOME
How is CML treated?
- Tyrosine kinase inhibitor (Imatinib)
- PCR monitoring of BCR:ABL
- Stem cell transplant
What are the side effects of Imatinib?
Pleural effusion, rash, cramps, vomiting, oedema
What is polycythemia vera and how does it present?
Overproduction of RBC by the bone marrow cells, causing the blood to thicken
- thrombosis, splenomegaly, often asymptomatic
- itch particularly after a hot shower
How is polycythemia investigated?
a) bloods
b) genetics
a) all cell lines high, low epo
b) JAK2 mutation
How is polycythemia vera treated?
- Aspirin to reduce clot risk
- Cytoreductive surgery
- Hydroxycarbamide
What is multiple myeloma and how does it present?
Neoplastic disease of plasma cells (B cells that produce antibodies. CRAB presentation - Calcium increased - Renal impairment - Anaemia - Bony lesions
BACK PAIN!!!
These are due to paraprotein clogging up various sites
What ethnicity have a higher proportion of patients with multiple myeloma?
African descent
What is the pathophysiology of multiple myeloma?
Plasma cells proliferate and produce paraprotein, a faulty monoclonal antibody.
How is multiple myeloma diagnosed?
Serum paraprotein (immunoglobulin electrophoresis)
Serum free light chain blood test
Blood film rouleax - increased plasma viscosity due to overproduction of immunoglobulins
How is multiple myeloma treated?
- Chemo
- Bisphosphonates
- Stem cell transplant
- Stop nephrotoxic drugs
What are the symptoms of iron deficiency?
Fatigue, leg cramps and craving ice
What are the symptoms of iron overload/haemochromatosis?
Chondrocalcinosis, iver cirrhosis, diabetes, cardiomyopathy, arthritis ‘bronzed diabetes’
What is the pathophysiology of primary haemochromatosis?
Mutation in HFE gene, so hepcidin isnt produced and too much iron is absorbed from the blood.
It is then stored in the liver and heart, where it causes cirrhosis and cardiomyopathy
What causes secondary haemochromatosis?
Chronic haemolysis, multiple transfusion, excess dietary
How is haemochromatosis treated? What investigation should you do to look for complications?
- Phlebotomy
- DFO/DFP (bind iron)
MRI for liver and heart
What is myelofibrosis?
Bone marrow disorder characterised by excessive fibrosis due to proliferation of an abnormal clone of haematopoietic stem cells
What are the primary and secondary types of myelofibrosis?
Primary - idiopathic
Secondary - develops from PV or ET (other myeloproliferative disorders)
What are the symptoms of myelofibrosis?
MASSIVE SPLENOMEGALY, bone pain, fatigue, bruising, sweats
What investigations should be done in myelofibrosis
a) bloods
b) blood film
c) bone marrow biopsy
Bloods - pancytopenia OR pancythemia
Blood film - tear drop poikilocytes/dacrocytes and nucleated RBCs
Biopsy - collagen fibrosis, JAK2/MLP/CALR mutation
How is myelofibrosis managed?
Generally incurable, except for stem cell transplant
Symptomatic treatment - transfusion, allopurinol, splenectomy, folic acid, JAK2 inhibitors
What are the symptoms of hereditary spherocytosis?
Splenomegaly, jaundice and fatigue, associated with cholecytisis
What is the pathophysiology of hereditary spherocytosis?
Patients have abnormally shaped but functioning inherited erythrocytes. The spleen attacks them (and becomes massive), causing anaemia with a high reticulocyte count
What would you expect from macrocytic anaemia and pancytopenia?
B12/folate deficiency
How is B12 deficiency managed?
If no intrinsic factor is present either, patient will need lifelong IM B12 (oral wont work due to lack of IF)
What factors are involved in the extrinsic pathway, and how is this measured?
7
PTT
What factors are involved in the intrinsic pathway, and how is this measured?
8,9,11,12
APTT