Haematology Flashcards
Aetiology of microcytic anaemia
Iron deficiency
Thalassaemia
Sideroblastic
Chronic disease (can be normocytic)
Aetiology of normocytic anaemia
Acute blood loss Anaemia of chronic disease Bone marrow failure Renal failure Hypothyroidism Haemolysis Pregnancy
Aetiology of macrocytic anaemia
B12 or folate deficiency (or anti-folate drugs) Alcohol excess or liver disease Reticulocytosis Cytotoxic drugs Myelodysplastic syndromes Marrow infiltration Hypothyroidism
When is transfusion in acute anaemia indicated?
<70g/L
How is red cell distribution width RDW useful in anaemia
If simultaneous pathology is occurring such as poor absorption of iron and folate (coeliac disease) then this may be shown in a greater volume distribution
Signs of chronic iron-deficiency anaemia
Koilonychia
Atrophic glossitis
Angular stomatitis
Post-cricoid webs (Plummer-Vinson)
Pathophysiology of anaemia of chronic disease
1) Poor use of iron in erythropoiesis
2) Cytokine induced shortening of RBC survival
3) Decreased production of and response to erythropoietin
Microcytic anaemia not responding to iron think
Sideroblastic anaemia
Ineffective erythropoiesis
Howell-Jolly bodies
Seen post-splenectomy and in hyposplenism
Causes of hyposplenism
Sickle-cell disease Coeliac diseaase Congenital IBD Myeloproliferative disease Amyloid
Reticulocytes
Young, large, immature RBC
Indicate active erythropoiesis
Increased in haemorrhage, haemolysis
Schistocytes
Fragmented RBCs in intravascular haemolysis- DIC, haemolytic anaemic syndrome, thrombotic thrombocytopenic purpura TTP, pre-eclampsia
Spherocytes
Autoimmune haemolytic anaemia or hereditary spherocytosis
When are target cells seen (Mexican hat cells)
Liver disease
Hyposplenism
Thalassaemia
Cabot rings
Pernicious anaemia
Lead poisoning
Bad infections
Macrocytic megaloblastic causes of anaemia
B12 and folate deficiency
Nuclear maturation is delayed compared with the cytoplasm
Non-megaloblastic macrocytic anaemia
Alcohol excess Reticulocytosis Liver disease Hypothyroidism Pregnancy
Antibodies in pernicious anaemia
Parietal cell antibodies in 90%
IF antibodies- more specific but less sensitive
When is the indirect Coombs test used?
Pre-natal testing to see if there are antibodies against RBCs that are free in the serum
Causes of haemolytic anaemia
Acquired Immune mediated- Coomb's + Coomb's -ve Microangiopathic haemolytic anaemia Infection- malaria Paroxysmal nocturnal haemoglobinuria
Hereditary Enzyme defects- G6PD deficiency Hereditary spherocytosis Hereditary elliptocytosis Haemoglobinopathy- sickle cell disease, thalassaemia
Warm AIHA
IgG mediated
Lymphoproliferative disease- CLL, lymphoma
Cold AIHA
IgM mediated, bind at lower temperatures
Often following infection
Associated with chronic anaemia, Raynaud’s
Haemolytic anaemia that is coomb’s direct test positive
AIHA
Drug-induced- penicillin, quinine
Acute transfusion reaction
Haemolysis of the newborn
Sickle cell vaso-occlusive crises precipitated by
Hypoxia
Cold
Dehydration
Infection
Hereditary haemorrhagic telangiectasia
Osler-Weber-Rendu syndrome
Abnormal blood vessel development in the cutaneous tissue and mucous membranes
Haemophilia A inheritance
X-linked recessive
50% of sons affected
50% of daughters carriers
Christmas disease
Haemophilia B
Liver disease bleeding pathology
Decreased synthesis of clotting factors
Decreased absorption of vit K
Abnormalities of platelet function
Alteplase MOA
Recombinant tissue plasminogen activator
Converts plasminogen into plasmin
Degrading fibrin cross-linking
Bind fibrin so localise to the area of the clot
Immune thrombocytopenia
Anti-platelet antibodies
IV immunoglobulin may be used to temporarily raise the platelet count- ie for pregnancy or surgery
PT factors tested
Extrinsic and common
I, II,V,VII,X
APTT factor tested
I, II, V, VIII, IX, X, XI, XII
How should crossmatch blood be taken?
From one patient at a time and labelled immediately
When is Fresh Frozen Plasma used?
To correct clotting defects
DIC, TTP, liver disease, when vitamin K would be too slow
Complications of transfusion
Early- within 24 hours
Acute haemolytic reactions, anaphylaxis, bacterial contamination, febrile reactions, allergic reactions, fluid overload, transfusion related acute lung injury
Delayed- after 24 hours
Infections, iron overload, post-transfusion purpura, potentially lethal fall in platelet count
What is a massive blood transfusion?
Replacement of an individuals entire blood volume within 24 hours
What is autologous blood transfusion?
Patients blood is stored pre-op for their own use later
TRALI management
STOP the transfusion
Give 100% oxygen
Treat as ARDS with respiratory and circulatory support and close monitoring for sepsis
Donor should be removed from donor panel
LMWH
Preferred preventative anticoagulant
Inactivated factor Xa but not thrombin
Half life 2-4 fold longer than standard heparin and response is more predictable
Unfractioned heparin MOA
Binds antithrombin- increasing ability to inhibit thrombin, factor Xa and IXa
Rapid onset and short half-life
How often do DOACs need monitoring?
Every 3 months an assessment and an annual blood test
Target INR for warfarin for PE/DVT/AF/aortic valve replacement
2-3
Target INR for warfarin for mitral valve replacement
2.5-3.5
INR 5-8, no bleed
Withhold warfarin and restart at lower dose once <5
INR 5-8 minor bleed
Stop warfarin and admit for urgent IV vit k
Restart warfarin <5 INR
INR >8 no bleed
Stop warfarin
Haematology advice
INR >8 minor bleed
Stop warfarin and admit for urgent IV vit k
Restart warfarin <5 INR
Daily check of INR
Any major bleed on warfarin
STOP warfarin
Give Prothrombin Complex Concentrate and IV vit K
Discuss with haematology
Types of leukaemia
Chronic lymphoblastic leukaemia
Chronic myeloid leukaemia
Acute lymphoblastic leukaemia
Acute myeloid leukaemia
Commonest cancer of childhood
Acute lymphoblastic leukaemia
Signs and symptoms of ALL
Marrow failure- anaemia, infection and bleeding
Infiltration- hepatosplenomegaly, lymphadenopathy- superficial or mediastinal, orchidomegaly, CNS involvement- cranial nerve palsies, meningism
Treatment for ALL
Educate and motivate patient to get involved with treatment
Support- blood/platelet transfusion, IV fluids, allopurinol (tumour lysis syndrome prevention)
Infections- immediate antibiotics and start neutropenic regimen
Chemotherapy
Philadelphia chromosome
Reciprocal change of information between 22 and 9
Results in chronic myeloid leukaemia and is associated with some forms of ALL
22t(9:22)
What are myelodysplastic syndromes?
Disorders that manifest as bone marrow failure- life threatening infection and bleeding
AML differentiated from ALL
Auer rods on biopsy
Commonest acute leukaemia in adults
AML
CML presentation
Mostly chronic and insidious- weight loss, tiredness, fever, sweats
Features of gout due to purine breakdown
Bleeding- anaemia and bruising
Abdominal discomfort from splenic enlargement
Most common leukaemia
Chronic lymphocytic leukaemia
Progressive accumulation of a malignant clone of functionally incompetent B cells
CLL presentation
Often none- surprise on a routine FBC
Can have constitutional symptoms or anaemic or infection prone
Enlarged, rubbery, non-tender nodes
Hepatosplenomegaly
Characteristic Hodgkin’s lymphoma cells
Reed-Sternberg cells
Risk factors for Hodgkin’s lymphoma
Affected sibling
EBV
SLE
Post-transplantation
Symptoms and signs of Hodgkin’s lymphoma
Enlarged, non-tender, rubbery, superficial lymph nodes- usually cervical but can be axillary or inguinal 25% have constitutional upset Alcohol induced lymph node pain Mediastinal lymph node involvement Cachexia, anaemia, organomegaly
Tests for Hodgkin’s lymphoma
Blood- FBC, film, ESR, LFT, LDH, urate, Ca2+
Imaging- CXR, CT TAP
Staging system used in Hodgkin’s lymphoma
Ann-Arbor system
MALT lymphoma
Mucosa-associated lymphoid tissue
Gastric is caused by H. pylori
Burkitt’s lymphoma
Non-Hodgkin’s lymphoma
Childhood disease
Characteristic jaw lymphadenopathy
Causes of polycythaemia
Relative- low plasma
Absolute- primary- Polycythaemia vera,
secondary- hypoxia or inappropriate erythropoietin secretion
Mutation in polycythaemia vera
JAK2
>95%
Presentation of polycythaemia vera
Asymptomatic and detected on FBC
or
Hyperviscosity related- headaches, dizziness, tinnitus, visual disturbance
Itching after a hot both and erythromelalgia (burning sensation in fingers and toes)
Signs
Facial plethora, splenomegaly, gout from increased urate from RBC turnover
Arterial or venous thrombosis may be present
Treatment of polycythaemia vera
Venesection to keep the risk of thrombosis down
Aspirin 75mg daily
If higher risk (>60 years old or previous thrombosis) then hydroxycarbamide
Alpha-interferon in women of childbearing age
Treatment for essential thrombocythaemia
Aspirin 75mg daily
Clinical features of myeloma
Osteolytic bone lesions- backache, pathological fractures, vertebral collapse
Hypercalcaemia- increased osteoclastic activity
Anaemia, neutropenia or thrombocytopenia from marrow infiltration by plasma cells
Recurrent bacterial infections
Renal impairment from light chain deposition in the distal loop of Henle
Tests for multiple myeloma
FBC, raised ESR, raised urea and calcium, alk phos normal unless healing fracture
Film
Bone marrow biopsy- increased plasma cells
Serum/urine electrophoresis
Xray- lytic lesions, pepperpot skull, vertebral collapse, fractures, osteoporosis
Treatment for multiple myeloma
Supportive- analgesia (avoid NSAIDs- renal function), bisphosphonate, local radiotherapy
Transfusion for anaemia
Renal failure- rehydration and ensure adequate fluid intake
Rapid infection control
Chemotherapy
Causes of massive splenomegaly
CML
Myelofibrosis
Malaria
Leishmaniasis
Protein C & S action
Vitamin K dependent factors that act together to cleave and neutralise factors V and VIII
Deficiency causes thrombophilia
Activated protein C resistance/ factor V leiden syndrome
Single point mutation in factor 5 so that this clotting factor is not broken down by APC
5 fold increase risk of DVT/PE if heterozygous
