Haematology Flashcards
(35 cards)
ANAEMIA: List the typical symptoms of patients with anaemia
- Fatigue
- Lethargy
- Pallor
- Dyspnoea
- Palpitations
- Chest pain
ANAEMIA: Classify anaemia in terms of red cell indices and list common causes of each type of anaemia.
ANAEMIA: Discuss the common causes of confirm iron deficiency anaemia.
- Dietary
- Blood loss (menstruation)
- Duodenum or proximal jejunum pathology that reduced absorption
- Pregnancy
ANAEMIA: Outline the clinical features and laboratory diagnosis of sickle cell anaemia
Clinical features:
- Sickle cell crisis1: Severe pain lasting up to 7/7
- Recurrent infections
- Anaemia (normocytic)
- Failure to thrive
Laboratory findings:
- High rectiulocyte count
- Howell-Jolly bodies (a nucleated cell which provide evidence of functional asplenia, due to the sickled cells becoming stuck in the spleen) and target cells on blood smear
- Iron levels are normal
- Abnormal haemoglobin forms on electrophoresis - HgS and HgSC
- Pathological basis: Defect in the beta chain of haemoglobin. Autosomal recessive condition
1: Symptoms arise due to the abnormally shaped cells blocking small blood vessels, reducing perfusion to distal sites which can in turn cause organ damage and increased vulnerabilty to infections (due to splenic damage)
ANAEMIA: Outline the clinical management of sickle cell crisis and the importance of sickle cell
Management of sickle cell crisis
- Analgesia: Paracetamol, NSAIDS or opioids as appropriate for pain level
- Supportive care and correction of cause:
- Oxygen if hypoxic, fluids and antibiotics if required
- Correct cause e.g. warming if hypothermic
- Blood transfusion for life-threatening vaso-occlusive events
ANAEMIA: Describe the laboratory features of haemolysis. Outline the causes of haemolytic anaemia and their treatment.
Laboratory findings:
- Normocytic anaemia
- MCHC elevated (due to lysed RBCs releasing haemoglobin)
- Increased reticulocyte count (as the body tries to increase RBC number)
- Abnormal forms on peripheral smear (schistocytes)
- Elevated LDH and unconjugated bilirubin due to increased RBC breakdown
- Low haptoglobin (becomes depleted in the presence of high concentrations of haemoglobin, as acts to bind free haem)
- Coomb’s test: Positive suggests an immune mediated cause (tests for IgG bound to the surface of RBCs)
Causes of haemolytic anaemia:
- Rhesus incompatibility
- ABO incompatibility
- Hereditary causes:
- RBC defects, enzymatic deficiencies, abnormal Hb (sickle cell), thalassaemia
- Acquired haemolytic anaemia:
- Immune mediated:
- Autoimmune antibodies in conditions such as SLE, RA and scleroderma
- Haemolytic disease of the newborn
- Non-immune mediated:
- Medication induced
- Infection
- HUS, DIC, TTP, HELLP syndrome
- Immune mediated:
Management of haemolytic anaemia
Coomb’s positive (immune mediated)
- Treat causes plus steroids
- Splenectomy1 plus rituximab (Monoclonal Ig against B cells)
- Whole obody plasmaphoresis
Coomb’s negative (not immune mediated) e.g. prosthetic valve haemlysis, TPP, hypersplenism
Congenital
1: Splenectomy is helpful as the spleen is the major site of RBC destruction
ANAEMIA: Outline the laboratory features of microangiopathic anaemia and list the common causes.
Microangiopathic haemolytic anaemia (MAHA) is where the small blood vessels have structural abnormalities that cause haemolysis of the blood cells travelling through them. Imagine a mesh inside the small blood vessels shredding the red blood cells. This is usually secondary to an underlying condition:
- Haemolytic Uraemic Syndrome (HUS)
- Disseminated Intravascular Coagulation (DIC)
- Thrombotic Thrombocytopenia Purpura (TTP)
- Systemic Lupus Erythematosus (SLE)
- Cancer
Laboratory findings:
- Schistocytes (products of RBC breakdown)
- ?Thrombocytopenia (platelet aggregation in vessels leads to haemolysis of RBCs)
ANAEMIA: Outline the features and causes of inherited red cell membrane defects and of red cell enzymopathies.
Features:
- Anaemia (haemolytic)
- Jaundice
- Gallstones (pigmented - due to the increased production of bilirubin)
- Splenomegaly (due to the increased breakdown of RBCs)
Causes:
- Hereditary Spherocytosis: Autosomal dominant. Sphere shaped, fragile RBCs which break easily when passing through the spleen.
- Hereditary Elliptocytosis: As above but oval shaped RBCs
- Thalassaemia: Defect in the alpha or beta chain of haemoglobin
- Sickle Cell Anaemia
- G6PD Deficiency: X-linked recessive. It causes crises that are triggered by infection, medications (antimalarials) or broad beans. Heinz bodies on blood film (can see bits of damaged haem attached to the sides of the RBCs)
ANAEMIA: Outline the clinical features and laboratory diagnosis of thalassaemia
Clinical features
- Microcytic anaemia
- Fatigue
- Pallor
- Jaundice
- Gallstones
- Splenomegaly
- Poor growth and development
- Pronounced forehead and prominent cheekbones
Laboratory diagnosis
- FBC - microcytic anaemia
- Haemoglobin electrophoresis reveals abnormal globin structure
- Elevated ferritin (iron overload can be seen in patients with thalassaemia)
THE WHITE CELL: Interpret a blood count showing a leucocytosis and list common causes for neutrophilia and neutropaenia, lymphocytosis and lymphopaenia.
THE WHITE CELL: Describe the clinical features of acute leukaemia and discuss the laboratory diagnosis.
THE WHITE CELL: Outline the general principles of treatment of acute leukaemias
Primarily treated with chemotherapy and steroids.
Bone marrow transplant if prognosis is poor or relapse. Bone marrow transplant is necessary for those with the philadelphia chromosome in ALL.
Supportive care:
- Hickman line for venous access
- High calorie diet
- Allopurinol to prevent chemo induced tumour lysis syndrome (reduces urate acid levels)
- Monitor potassium and phosphate levels
- Monitoring for neutropenic sepsis - temperature >38 degrees on 2 occasions more than an hour apart → start abx (cephalosporin plus gentamicin)
THE WHITE CELL: Describe the clinical features and laboratory diagnosis of chronic leukaemias and outline the principles of management.
THE WHITE CELL: Outline the clinical presentation of leukaemias and key ddx
THE WHITE CELL: Describe the clinical features and laboratory diagnosis of multiple myeloma. Outline the associated laboratory abnormalities
Clinical features: C.R.A.B.
- Calcium: Hypercalcaemia
- Renal: Impaired renal function due to light chain deposition
- Anaemia: Due to bone marrow failure. Other consequences of bone marrow failure include recurrent infections and increased bleeding/bruising
- Bone: Osteolytic bone lesions due to osteoclast activation (backache, pathological fractures)
- Increased viscosity of blood
Laboratory diagnosis:
- Monoclonal band/paraprotein (representative of excessive production of a single Ig)
- Urine Bence-Jones protein postive
- FBC: Normocytic normochromic anaemia, leukopenia
- Blood film: Rouleaux formation (stacks of RBCs)
- Raised ESR and calcium
- Deranged U&Es
- ‘Pepper pot’ skull on skeletal XR
THE WHITE CELL: Describe the clinical features of lymphoma. Classify lymphomas into Hodgkin’s and Non-Hodgkin’s disease and to high- and low- grade groups. Outline the principles of treatment.
Clinical features: (typically the same for Hodgkin’s and Non-Hodgkin’s)
- Lymphadenopathy
- Non-tender and rubbery
- Classically in the neck, axilla or inguinal region
- Pain after alcohol ingestion
- B symptoms: Weight loss, night sweats, fever
- Fatigue
- Cough
- Dyspnoea
- Recurrent infections
- Mediastinal lymph nodes can have mass effects (SVC/bronchial obstruction)
- Hepatosplenomegaly
Hodgkin’s lymphoma
- Characterised by Reed-Sternburg cells (Owl eyes)
- ~ 15% of cases
- Slow growing, localised and rarely fatal
- Consider risk factors (EBV, SLE, obesity, FHx)
Non-Hodgkin’s lymphoma
- Includes all lymphomas without Reed-Sternburg cells
- Can be classified into:
- High grade: Divide rapidly, rapid onset. More aggressive but have better prognosis if identified and treated
- Low grade: Divide slowly with a more insidious onset. Tend to be widely disseminated at presentation and incurable.
- Can present with symptoms of extra-nodal disease (in 25%): Oropharynx, skin, CNS, gut or lung
- Burkitt’s - associated with EBV, malaria and HIV
- MALT lymphoma - associated with H.Pylori infection (?Hx of dyspepsia)
Investigations
- FBC, U&Es, ESR, LFT, calcium
- LDH - elevated
- Lymph node biopsy is diagnostic
- CT, MRI and PET for diagnosing and staging tumours
Principles of treatment
- Ann Arbor staging is use for staging
- Chemotherapy, radiotherapy or chemo-radiotherapy
THE PLATELET: Discuss the role of platelets in the pathophysiology of vascular disease including vascular thrombosis and platelet emboli
Role of the platelet:
Endothelial damage → exposure of collagen and vWF → platelet adhesion → synthesis of TXA2 by platelets to cause vasoconstriction and further aggregration → activation of the coagulation cascade to allow for the formation of fibrin
Role of pathophysiology:
Involved in the formation of thrombi, such as those causing MI, cerebrovascualar events and acute limb ischaemia
THE PLATELET: Describe the mechanism of action of aspirin and outline its role in cardiovascular disease prevention.
Aspirin MoA:
Inhibits COX-1, preventing the synthesis of pro-thombotic prostaglandins (activate the coagulation cascade)
Role in CVD:
- Reduces the risk of thrombus formation
Indications for aspirin:
- Prophylaxis of CVD
- Secondary prevention following MI: DAPT with aspirin and clopidogrel for 1 year, with aspirin continued
- Acute stroke (300mg), with switch to clopidogrel +/- anticoagulant after 2/52
- PVD
THE PLATELET: Outline the clinical features, investigation and treatment of immune thrombocytopaenia.
Clinical features:
- Purpuric rash
- Bruising
- Bleeding - epistaxis, menorrhagia, melaena
- Splenic
- In children: Usually follows viral infection. Tends to be acute and self limiting
- In adults: Less acute. Normally in women with other autoimmune diseases
Investigation:
- FBC: Thrombocytopenia
- Platelet autoantibodies
Treatment:
- Corticosteroids (prednisolone)
- IV immunoglobulin
- Rituximab (targets B cells)
- 2nd line: Splenectomy
HAEMOSTASIS: Describe the laboratory tests to assess the clotting system and recognise and interpret patterns of abnormality.
- aPTT - intrinsic pathway
- Used to monitor heparin therapy
- aPT - extrinsic pathway
- Increased by hepatic disease or warfarin use
- Used as INR
- Thrombin time (addition of thrombin to pts blood)
- Prolonged in fibrinogen deficiency/dysfunction
HAEMOSTASIS: Outline a plan of investigation for a patient complaining of easy bruising.
- FBC: Platelet count, panctopenia suggestive of leukaemia
- PT, PTT, thrombin time
- Look for infective cause: CRP, ESR, WCs
- Check for haemophilia with PTT
HAEMOSTASIS: Describe the role of the liver in normal clotting, including the role of vitamin K in the synthesis of some clotting factors
Liver produces clotting factors
Vitamin K is required for the production of clotting factors II, VII, IX and X.
- Deficiencies in vitamin K can arise from malabsorptive conditions (fat soluble), cholestatic jaundice (no bile salts) or antibiotics (gut flora disturbances)
Inhibitors of coagulation
- Anti-thrombin III: Potentiated by heparin
- Activated protein C and protein S: Induce fibrinolysis by destruction of factors V and VIII
Fibrinolysis
- Tissue plasminogen activator (t-PA) converts plasminogen to plasmin.
- Plasmin breaks down fibrinogen and fibrin, producing degradation products such as D-dimer
- Mediators, such as thrombin and protein C, stimulate the release of t-PA
HAEMOSTASIS: Discuss the clinical features, diagnosis and management of inherited bleeding disorder including haemophilia and von Willebrands disease.
Haemophilia
Haemophilia A - factor VIII deficiency and Haemophilia B - factor IX deficiency
- X-linked recessive
- Raised aPTT and low clotting factor
Clinical features:
- Major bleeds after minor trauma
- Recurrent haemarthroses, leading to crippling arthropathies
Management
- Avoids NSAIDs and IM injections
- Minor bleeding:
- Compression and elevation
- Desmopressin to raise factor VIII may be sufficient
- Major bleeding:
- Recombinant factor VIII/IX to raise factor level to 50% of normal
Von Willebrands Disease
May be autosomal recessive or dominant.
Diagnosis:
- aPTT increased
- INR and platelets normal
Clinical features:
- Features of a platelet type disorder - epistaxis, menorrhagia
Management:
- Transexamic acid for mild bleeding
- Desmopressin and recombinant factor VIII1 for more severe bleeds
1: As vWF has a secondary role of binding factor VIII to prevent degradation. So low factor VIII levels co-exist
HAEMOSTASIS: Discuss the pharmacokinetics and clinical use of warfarin including laboratory tests used to monitor clinical effect.
Pharmacokinetics of warfarin
- Requires bridging treatment with heparin until INR is within the therapeutic range as takes up to 5/7 to have an effect on clotting factors
- INR measured on alternate days
Monitoring
- INR
