Haematology Flashcards
What is the origin of platelets? What type of storage granules do they contain?
Megakaryocytes- come from the common myeloid precursor in haematopoesis.
3 types of storage granules:
- alpha: contain clotting factors
- dense: contain mediators of platelet activation eg. serotonin
- glycogen- provide energy
Which factors are involved specifically in the extrinsic pathway of secondary haemostasis?
Tissue Factor
Factor 7
Which factors are involved specifically in the intrinsic pathway of secondary hemostasis?
Factor 12
Factor 11
Factor 8
Factor 9
Which clotting factor is deficient in:
A- Hamophilia A
B- Hamophilia B
C- Hamophilia C
A- Factor 8
B- Factor 9
C- Factor 11
Which of the clotting factors are vitamin k dependant?
2 (prothrombin), 7 (extrinsic), 9 (intrinsic) and 10
How does Warfarin work?
Prevents intrinsic and extrinsic clotting cascade by inhibiting the synthesis of Vitamin K dependent clotting factors (Prothrombin, 7, 9 and 10)
How does Apixaban work?
Prevents intrinsic and extrinsic clotting cascades by inhibiting factor 10a.
What is fibrinolysis?
The process by which the fibrin clot is degraded.
How does the body prevent unwanted clots?
- Protein C in the venous circulation (activated by thrombin) degrades 5a and 8a.
- Natural heparins on the endothelial cell surfaces enhance the release of prostacyclin, and also the activity of anti-thrombin.
What are the 2 main blood tests for clotting?
- Prothrombin time- tests the extrinsic pathway
2. Activated partial prothrombin time- tests the intrinsic pathway.
What normally prevents platelets from adhering to endothelial cells?
- Nitrous oxide
- Prostacyclin
PREVENT platelets from adhering to endothelial cells.
What are acanthocytes?
RBCs with spikes on surface
In which conditions may acanthocytes be present in the blood?
Splenectomy
Alcoholic liver disease
Spherocytosis
What are blasts?
Nucleated precursors
In which conditions may blasts be present in the blood?
Leukaemia
Myelofibrosis
What are Burr cells and In which conditions may they be present in the blood?
RBCs with surface projections, present in:
Renal failure
Liver failure
What is a Cabot ring and in which conditions may they be present in the blood?
Thin red/ purple ring in a RBC, present in:
Pernicious anaemia
Lead poisoning
Bad infections
Which condition may have cells with Auer rods present?
AML
Which conditions have hypochromic RBCs?
Iron deficiency anaemia
Thalassaemia
What are the blood film features in iron deficiency anaemia?
- Pencil cells
- Hypochromic RBCs
- Target cells
- Microcytic RBCs
- Decreased ferritin
What are the blood film features in haemolytic anaemia?
- Spherocytes
- Reticulocytes
- Tear shaped RBCs
- Normocytic/ macrocytic
What are the blood film features in B12/ folate deficiency?
- Macrocytic RBCs
2. Hypersegmented neutrophils (6-8 lobes)
When are tear drop shape RBCs found?
Extra-medullary haematopoeisis eg. Myelofibrosis, haemolysis
When are target cells seen?
- Iron deficiency anaemia
- Thalassaemia
- Liver disease
- Hyposplenism
What are spherocytes and in which conditions may they be present?
Spherical hyperchromic RBCs:
- Hereditary spherocytosis
- AIHA
What are schistocytes and in which conditions may they be present?
Fragmented RBCs which have been sliced by fibrin
DIC
Thrombotic thrombocytopenic purpura
What are reticulocytes and in which conditions may they be present?
Large young RBCs
Haemolytic anaemia
How are blood tests affected in DIC?
APTT increased PT (INR) increased TT increased D-dimer increased Platelet count decreased Presence of schistocytes
How are blood tests affected in Haemophilia?
APTT increased
How are blood tests affected in VWD?
APTT increased
How are blood tests affected in Vitamin K deficiency?
PT and APTT increased
How are blood tests affected in liver disease?
PT increased
APTT increased
Platelet count may decrease
What are the characteristics of Haemophilia?
Bleeding into joints
Bleeding into muscles
What are the characteristics of Von Willebrand disease?
Bleeding
Epistaxis
Usually less severe than Haemophilia
What is desmopressin used for?
Managing haemophilia and Von Willebrands disease
Which triad may be present in Haemochromatosis?
- Tanned skin
- Cirrhosis
- Diabetes
What is haemochromatosis?
Excessive intestinal absorption of iron
Iron overload and accumulation in tissues (liver, adrenals, heart, skin, pancreas)
Which gene is usually mutated in hereditary haemochromatosis and how is this inherited?
Autosomal recessive inheritance- mutations in HFE gene
Which factors promote fibrinolysis?
- Thrombin induces the release of TPA which converts plasminogen to plasmin. Plasmin helps to break the fibrin mesh
- Thrombin also stimulates the production of anti-thrombin: which inhibits the production of thrombin and factor 10a, 9a and 11a.
Which myeloproliferative neoplasm affects WBCs?
CML
Which myeloproliferative neoplasm affects RBCs?
Polycythaemia vera
Which myeloproliferative neoplasm affects platelets?
Essential thrombocythaemia
Which myeloproliferative neoplasm affects fibroblasts?
Myelofibrosis
Most myeloproliferative neoplasms have an abnormality in which gene?
JAK2
Which myeloproliferative neoplasm may present with headaches, facial plethora, burning sensation in fingers and toes, and tinnitus?
Polycythaemia vera
In polycythaemia vera, there is excess production of ______
RBCs
WBCs
Platelets
In polycythaemia vera there is increased risk of __________
Hyperviscosity Venous thrombi (DVT, PE), arterial thrombi (MI)
Other than polycythaemia vera, what are the other causes of polycythaemia (increased RBC production)?
- Hypoxia
2. Excess EPO hormone
How can polycythaemia vera be treated?
- Venesection
- Aspirin
- Hydroxycarbamide for thrombocytosis
What are the 3 main consequences of essential thrombocythaemia?
- Bleeding
- Thrombi (Arterial or venous)
- Microvascular occlusion
Microvascular occlusion is a consequence of thrombocythaemia and can cause symptoms such as…..
Headache Blurred vision Chest pain Digital ischemia Burning in fingers/ toes (erythromelalgia)
What are the differentials for essential thrombocythaemia?
Cancer
Chronic inflammation
Past surgery
The BCSH criteria are used for diagnosing…..
Essential thrombocythaemia
Essential thrombocythaemia can be treated using ……….
- Aspirin
2. Hydroxycarbamide
In __________ there is clonal proliferation of megakaryocytes causing platelet counts of >1000 with abnormal functioning platelets.
Essential thrombocythaemia
What is myelofibrosis?
Clonal proliferation of fibroblasts
Bone marrow fibrosis
Leads to extramedullary haematopoiesis (spleen and liver)
What are the consequences of myelofibrosis?
- Anaemia
- Infection
- Extramedullary haematopoeisis
If a patient presented with the following symptoms what may the diagnosis be?
B symptoms (fever, night sweats, weight loss)
Anaemia
Infections
Enlarged spleen
Gout
Myelofibrosis
How does myelofibrosis appear on blood films?
- Tear drop shape RBCs
2. Nucleated RBCs (leukoerythroblastic cells)
Ruxolitinib is an oral JAK2 inhibitor, used for managing ___________. It causes decreased nightsweats and reduction in splenomegaly.
Myelofibrosis
The BCR:ABL translocation is most commonly present in which condition?
CML
How can AML and CML be distinguished on blood film?
AML:
- Auer rods
- Myeloblasts
- Monoblasts
CML:
- High cell count (hypercellular marrow)
- Raised eosinophils
- Raised basophils
Which type of leukaemia is most common in children?
ALL
What are the 3 phases of CML?
- Chronic phase
- Accelerated phase
- Blast transformation
What are the myelodysplastic syndromes?
Group of disorders which present as bone marrow failure (anaemia, neutropenia and thrombocytopenia)
What is the pathogenesis of myelodysplastic syndromes?
MDS arises in haematopoietic stem cells
Abnormal cells produced due to a partial block in differentiation
Blasts may accumulate
How can myelodysplasia be diagnosed on blood film?
Pancytopenia
Increased marrow cellularity
Ring sideroblasts
How may myelodysplasia be treated?
- Transfusion of RBCs or platelets
- EPO
- G-CSF
- Allogenic stem cell transplant
If a patient presented with the following 3 symptoms what may be the diagnosis?
- Jaundice
- Hepatosplenomegaly
- Pigment gallstones
Haemolytic anaemia
What is the direct Coombs test used for?
Autoimmune haemolytic anaemia
detects antibodies for RBCs. Agglutination = positive test result
When is the indirect Coombs test used?
Prenatal testing
Before blood transfusion
Detects anti RBC antibodies free in serum
Warm AIHA is mediated by ____
IgG
Cold AIHA is mediated by ____
IgM
How is warm autoimmune haemolytic anaemia treated?
- Steroids
- Rituximab
- Potential splenectomy
How is cold autoimmune haemolytic anaemia treated?
- Keep warm
- Blood transfusions
- Chlorambucil
What are the ACQUIRED types of haemolytic anaemia?
- Autoimmmune (warm or cold)
- Drug induced
- Infection
- Microangiopathic haemolytic anaemia
What are the HEREDITARY types of haemolytic anaemia?
- Enzyme defects eg. GP6D deficiency, pyruvate kinase deficiency
- Membrane defects eg. Hereditary spherocytosis
- Haemogobinopathys eg. Thalassaemia, Sickle cell
Which type of haemolytic anaemia will be Coombs test POSITIVE?
Autoimmune haemolytic anaemia (acquired)
What happens to iron, ferritin and total binding capacity in IDA?
Iron decreases
Ferritin decreases
TIBC increases
What happens to iron, ferritin and total binding capacity in anaemia of chronic disease?
Iron decreases
Ferritin increases
TIBC decreases
What happens to iron, ferritin and total binding capacity in haemolytic anaemia?
Iron increases
Ferritin increases
TIBC decreases
_______ inhibits iron absorption by binding ferroportin, causing it to become internalised.
Hepcidin
In inflammation/ infection, Il-6 is released, causing Hepcidin to be switched ___
ON
Sickle cell anaemia is caused by a genetic polymorphism in the _______ gene, causing Glu -> Val translocation, leading to HbA -> HbS.
Beta globin
What happens to HbS when it is deoxygenated?
It polymerises, causing RBCs to deform and block small vessels, leading to ischemic pain.
What are the potential complications of sickle cell anaemia?
- Vaso-occlusive crises
- Infections
3, Hyposplenism- pneumococcus, meningococcus - Acute chest syndrome
- End organ damage
Which type of Thalassaemia is more common?
Beta thalassaemia
When does Beta Thalassaemia usually present?
Aged under 1 year
Newborn has HbF but this declines in levels
Present with severe anaemia and failure to thrive
Alpha thalassaemia major/ Hb Barts usually results in _________
Death in utero
What are some inherited causes of thrombophilia?
- Protein C & S deficiency
- Factor V Leiden
- Anti thrombin deficiency
What are some acquired causes of thrombophilia?
- Oral contraceptive pill
2. Antiphospholipid syndrome
What is myeloma?
Monoclonal proliferation of plasma cells in bone marrow
Leads to IgG/ IgA secretion (paraprotein) which can’t function properly
What are the clinical features of myeloma? (CRABI)
C- Hypercalcaemia R- Renal impairment A- Anaemia, neutropenia and thrombocytopenia B- Bone pain and destruction I- Infection
How can myeloma be diagnosed?
- Monoclonal protein band on electrophoresis of blood or urine
- Plasma cells >10% in marrow
- Organ damage: anaemia, hyperkalaemia, renal failure
- Xrays: bone lesions
What are the complications of myeloma?
- Hypercalcaemia: renal stones, brittle bones
- Anaemia
- Spinal cord compression
- Hyperviscosity
- AKI
Which bones does myeloma often affect?
Pelvis
Spine
Ribs
Shoulders
How can myeloma be treated?
- Analgesia
- Bisphosphonates (Zoledronate) slow down osteoporosis
- Blood transfusions
- Iv immunoglobulins
- Chemotherapy (Lenalidomide, Dexamethosone, Velcade)
- Autologous stem cell transplant
Give examples of microcytic anaemia.
Iron deficiency anaemia
Haematinic deficiencies- sickle cell, thalassaemia
Lead poisoning
Anaemia of chronic disease
Give examples of normocytic anaemia
Anaemia of chronic disease Bone marrow failure Acute blood loss Renal failure Aplastic anaemia
Give examples of macrocytic anaemia.
Megaloblastic: B12 or folate deficiency Alcohol Hypothyroidism Haemolytic anaemia Liver disease Myelodysplasia Serum paraprotein
Monoclonal gammopathy of unknown significance significance usually preceeds _________.
Myeloma
What is the lower limit of the Hb reference range for women?
120g/L
What is the lower limit of the Hb reference range for men?
130g/L
Which protein effluxes iron into the blood from enterocytes?
Ferroportin
What are the causes of iron deficiency anaemia?
Poor dietary intake
Poor absorption: Crohn’s, coeliac
Iron loss: GI bleeding, menorrhagia
Increased requirement: pregnancy
Which drugs may cause folate deficiency?
Methotrexate
Phenytoin
The majority of B12 is absorbed by binding ________ and being absorbed in the terminal ileum.
Intrinsic factor
What is pernicious anaemia?
Autoimmune gastritis meaning a lack of intrinsic factor secreted from parietal cells
Poor absorption of Vitamin B12
Which blood group is the universal donor of RBCs?
Group O neg
Which blood group is the universal recipient of RBCs?
Group AB positive
What is the most common blood group in Caucasians?
Group O
Which Ig antibodies against RBCs cause extravascular haemolysis slowly?
IgG
Which Ig antibodies against RBCs cause acute and dramatic intravascular haemolysis?
IgM
How does forward blood typing work?
Patients RBCs added to antibodies
If agglutination appears = patients RBCs has those antigens
ANTIGEN SCREENING
How does reverse blood typing work?
Patients plasma is added to RBCs
Used to detect which antibodies are in the patients serum
ANTIBODY SCREENING
Which type of blood product is stored for <35days at 4degrees?
RBCs
Which type of blood product is stored for <7days at 22degrees?
Platelets
Which type of blood product is stored frozen?
Plasma
What is the volume of the average bag of donor blood?
274ml
What are the 4 types of blood product that can be transfused?
- RBCs
- Platelets
- Plasma (FFP)
- Cryoprecipitate (frozen fibrinogen replacement)
How long should a bag of RBCs be transfused over?
2-3 hours
How long should a bag of platelets be transfused over?
30 mins
What is the definition of major haemorrhage?
- Loss of >50% total blood in <3 hours
- Loss of whole blood volume over 24 hours
- Loss of >150ml/minute
What are the 3 most SERIOUS risks of blood transfusion?
- ABO incompatibility
- Bacterial contamination
- Anaphylaxis
What are the 3 most COMMON risks of blood transfusion?
- Transfusion associated circulatory overload (TACO)
- Allergy
- Febrile non haemolytic transfusion reaction (delayed)
How many pooled donations are used in a bag of platelets?
4
or 1 apheresis
How many pooled donations are used in a bag of cryoprecipitate?
2
Which haematological cancer presents with B symptoms, cervical/axillary lymphadenopathy and alcohol related lymph node pain?
Hodgkin’s lymphoma
The Ann Arbor system is used to stage which haematological cancer?
Hodgkin’s lymphoma
Which chemotherapys are used for Hodgkin’s lymphoma?
A- Adriamycin
B- Bleomycin
V- Vinblastine
D- Dacarbazine
Which drugs make up the RCHOP regimen for high grade NHL lymphoma treatment?
R- Rituximab C- Cyclophosphamide H- Hydroxydaunomycin O- Oncovin (Vincristine) P- Prednisolone
Rituximbab and Chlorambucil are used to treat low grade ________
Non Hodgkin’s Lymphoma
Thrombopoeitin usually stimulates __________
Platelet production
Which clotting factor does von willebrand bind?
Factor 8
What is aplastic anaemia?
Bone marrow failure
Bone marrow stem cells disappear leaving fat spaces
Serum LDH is raised in which type of anaemia?
Haemolytic anaemia
Which antibody is secreted in breast milk?
IgA
IgA deficiency leads to an increased susceptibility to which type of bacteria?
Giardia lamblia
Bernard-Soulier syndrome is an autosomal recessive bleeding disorder caused by a deficiency in the platelet glycoprotein complex Ib-IX-V, which would normally bind to __________________________ to allow platelet adherence.
von Willebrand factor (vWF)
Thrombocytopenia is ______
Abnormally low numbers of platelets
DiGeorge syndrome involves failure of the thymus and can be rememberd by the mnemonic CATCH:
C-Cardiac abnormalities A- Abnormal facial expression T- Thymus failure C- Cleft palate H- Hypoparathyroidism
Ring Sideroblasts are a feature of which condition?
Myelodysplastic syndromes
What is the chance of contracting HIV from a needle stick injury?
0.3%
What is the chance of contracting HepC from a needle stick injury?
3%
What condition presents with:
- Neurological symptoms (headache, confusion)
- AKI
- Fever
- Low platelets
- Microangiopathic haemolytic anaemia
Thrombotic thrombocytopaenic purpura
Smear cells on blood film are characteristic of which haematological cancer?
CLL
CD19, CD10 and CD5 are markers of which type of cell?
Lymphocytes
Pale proliferation centres and an increase in lymphocytes is associated with which haematological cancer?
CLL
Lenalidomide, Dexamethosone and Velcade are used for which haematological disorder?
Myeloma
ADAMTS13 is attacked, preventing its maintenance breakage of VWF in which condition?
TTP