Haem Flashcards
Causes of a microcytic anaemia (low MCV) vs Normocytic (normal MVC) 80-100 vs Microcytic
Microcytic anaemia (FAT)
1) Fe deficiency (low ferritin)
2) Anaemia of chronic disease e.g. RA. (normal/high ferritin)
3) Thalassaemia (alpha or beta)
Normocytic anaemia
Infection, inflammation, malignancy duh
- also anaemia of chronic disease
1) Anaemia of chronic disease, acute blood loss
2) Haemolysis, hypothyroid
3) Failure - BM (aplastic anaemia), Renal
4) Pregnancy
Macrocytic anaemia
1) Megaloblastic - folate/B12 deficiency
2) Non megaloblastic - Alcohol, Haemolysis
Blood findings in Fe deficiency anaemia
Symptoms/signs
Treatment
including dose, duration and side effects
Low ferritin (iron storage) High transferrin
Blood film: Microcytic, hypo chromic
- Variation in size (anisocytosis)
- Variation in shape (poikilocytosis)
- Pencil cells
Signs
- Pallor, lethargy, SOB
- Atrophic glossitis; Angular stomatitis (cheilitis)
- Koilonychia (spoon shaped nails)
- Post cricoid webs (Plummer vinson syndrome)
Treatment
65 mg elemental iron (ferrous sulphate 200 mg) 3x daily
- Recheck Hb in 4 weeks (should go up by
- Continue at least 3 months after Hb normalises
Side effects of ferrous sulphate: Nausea, abdominal discomfort, diarrhoea or constipation, black stool
Petechiae cause
Differential diagnosis
Thrombocytopenia (low platelets)
Leukaemia Meningococcal septicaemia Vasculitis Henoch-Schonlein Purpura (HSP) Idiopathic Thrombocytopenia Purpura (ITP) Non-accidental injury
B12 deficiency
Causes
Clinical features
Investigations
Causes:
Low intake - vegan (found in meat, fish and dairy)
Low absorption - Pernicious anaemia (antibodies against IF/Parietal cells), Ilieal resection, Chron’s, bacterial overgrowth, tape worms
Importance of B12
B12 helps synthesize thymidine, and hence dna, so in deficiency RBC production is slow. Untreated, it can lead to megaloblastic anaemia and irreversible CNS complications
Clinical features
- General: Jaundice (due to haemolysis), glossitis, angular stomatitis
- Neuro: Irritability, depression, psychosis
- Spinal cord degeneration: Paraesthesiae, peripheral neuropathy. Also subacute combined degeneration of the spinal cord, a combination of peripheral sensory neuropathy with both upper and lower motor neuron signs due to ↓b12. The patient may display the classical triad of:
(1) Extensor plantars (UMN)
(2) Loss of knee jerk (LMN)
(3) Loss of ankle jerk (LMN)
Pernicious anaemia - what is it
Blood results
Management
Autoimmune condition in which atrophic glossitis –> lack of IF secretion from parietal cells of the stomach. Dietary B12 remains unbound and so can’t be absorbed in terminal ileum
Blood results
- Microcytic anaemia
- Low serum B12
- Hypersegmented neutrophils (>5 losses) = megaloblastic anaemia
- Parietal cell antibodies found in 90%
- IF antibodies, specific for PA but lower sensitivity
Management (of B12 deficiency)
- Treat the cause if possible
- If due to malabsorption - IM Hydroxocobalamin (B12) 1mg IM alternate days for 2 weeks, then every 3 months for live
- If due to poor oral intake: Oral B12 after the initial IM course (50-150mcg daily between meals)
What is thalassaemia?
What is beta thalassaemia
Types of beta thalassaemia
- for the worst give signs, blood film, electrophoresis, treatment
Genetic diseases of unbalanced Hb synthesis, with underproduction (or no production) of one globin chain. Unmatched globing precipitate, damaging RBC membranes, causing their haemolysis while still in the marrow
Beta thalassaemia: Point mutations in beta globin genes on chromosome 11
1) Beta thalassaemia minor/trait (heterozygous trait)
- Usually asymptomatic
- Mild, well tolerated anaemia (Hb >90) - may worsen in pregnancy
- MCV <75, HbA2 >3.5%, slight increase in HbF
2) Beta thalassaemia intermedia
- Moderate anaemia but not requiring transfusion
- May be splenomegaly
- Causes: Mild homozygous mutations, co inheritance with another trait e.g. HbC thalassaemia
3) Beta thalassaemia major
- Significant abnormalities in both beta-globin genes
- Presents in 1st year: Severe anaemia + FTT
- Extra-medullar Haematopoesis: RBCs made outside marrow: Skull bossing + hepatosplenomegaly (due to haemolysis)
- Osteopenia
- Life long blood transfusions needed - iron overload seen in 10yrs as endocrine failure (pituitary, thyroid, pancreas –> DM), liver disease and cardiac toxicity
- Blood film: Hypochromic anaemia, Target cells, Increased reticulocyte count
- Hb electrophoresis: ⇈HbF, HbA2 variable, HbA absent
CLL
Staging system
Symptoms
Signs
Blood results
Disease progression
Rai staging
0Lymphocytosis alone
Median survival >13yrs
I Lymphocytosis + lymphadenopathy
Median survival 8yrs
IILymphocytosis + spleno- or hepatomegaly
Median survival 5yrs
III Lymphocytosis + anaemia (Hb <110g/L)
2yrs Median survival
IV Lymphocytosis + platelets <100 × 109/L
1yr Median survival
Symptoms - Often non - surprise on routine FBC - May have anaemia, infection prone, or weight loss/anorexia/night sweats if severe Signs - Enlarged rubbery lymph nodes - Splenomegaly, hepatomegaly
Bloods
↑Lymphocytes—may be marked
Later: autoimmune haemolysis, marrow infiltration: ↓Hb, ↓neutrophils, ↓platelets.
Smear cells
Natural history - commonest leukaemia
⅓ never progress (or even regress), ⅓ progress slowly, and ⅓ progress actively. cd23 and β2 microglobulin correlate with bulk of disease and rates of progression. Death is often due to infection or transformation to aggressive lymphoma (Richter’s syndrome).
differential for enlarged spleen
- enlarged left kidney; unless enormous, there is resonance over the swelling anteriorly as it is covered by the gas containing colon
- carcinoma of the cardio or upper part of the body of the stomach; by the time it’s this big they were usually symptoms of gastric obstruction
- enlarged left lobe of the liver
Classification for enlargement of the spleen
massive splenomegaly causes
1.infections Dash viruses: glandular fever Dash bacterial: Typhus, typhoid, septicemia - Protozoa,: malaria, schistosomiasis - Parasitic: Hydatid
- Hematological disease
- leukemia: CML & CLL
- lymphoma: Hodgkins and non-Hodgkin’s
- Milo fibrosis, I TP, polycythemia rubra vera
- Hemolytic anemia is: e.g. spherocytosis, beta thalassemia - Portal hypertension
Increased pressure in the portal system causes progressive enlargement spleen and may lead to hypersplenism [e.g. excess removal of platelets resulting in thrombocytopenia] - Metabolic and collagen disease disease
- Amyloid Secondary to our ARA, collagen disease, chronic sepsis
- storage disease is e.g. Gaucher’s disease - Cysts, abscesses and tumors of the spleen
All uncommon
massive splenomegaly CML Myelofibrosis Lymphoma Polycythemia Portal hypertension
Indications for splenectomy
complications
Indications Rupture Hematological disease Tumors insists Part of another procedure e.g. radical excision of stomach cancer, distal pancreatectomy, splenorenal anastomosis For portal hypertension
complications
- Gastric dilation
- Thrombocytosis: DVT and PE risk. Antiplatelets like aspirin are given a prophylaxis in addition to MMWH
- Post splenectomy sepsis ( in capsulated microorganisms especially) - Immunization with Nakul, meningococcal an H influenza type B vaccines should be given preop. Adult should have penicillin for at least two years after splenectomy (Children get it until they are adults]. Annual flu vaccine also.
Howell-jolly bodies
What do they look like
Cause
Nuclear remnant in circulating erythrocytes
Hyposplenism
Heinz bodies cause
Other things seen on blood film
G6PD deficiency
Irregularly contracted cells
Schistocytes causes
MAHA
Prosthetic valve
Target cells
What do they look like
Causes
Targets?
Hyposplenism
Thalassaemia
Liver disease
Pencil cells cause
Iron deficiency anaemia
Basophilic stippling causes
Thalassaemia
Lead poisoning
Reticulocytes causes
Haemolysis
Haemorrhage
MM
PP
Features
Diagnosis
Investigations
Management
Prognosis
Epidemiology
M=F
~70yo
PP
Clonal plasma cell proliferation –> monoclonal Ig (IgA or IgG)
- Clones may produces light chains excreted by kidneys –> renal insufficiency
- Clones produce IL-6 which inhibits osteoblasts and activates osteoclasts
Features Renal insufficiency Hypercalcaemia Anaemia Bone - vertebral collapse, path fracture, bone pain
Diagnosis Clonal BM plasma cells >/= 10% Presence of se/urinary monoclonal protein End organ damage Calcium >2.6 Anaemia 10 Renal insufficiency Bone involvement
Investigations
Urine - high specific gravity; Electrophoresis - BJP
FBC: Anaemia; ESR: high; Ca: high; ALP normal
Blood film: rouleaux cells +/- plasma cells +/- cytopaenias
Renal function
Bone profile - inc calcium
X-rays: Pepper pot skull, and as above, punched out lytic lesions
Trephine BM biopsy
Management 1) Supportive Calcium: Hydrate, bisphosphates ?frusomide Renal: Hydrate, dialyse Anaemia: Transfuse, EPO Bone: Bisphosphonates Infections: Broad spectrum abx, ?IVIg
2) Specific - based on fitness
- fit: induction chemo then BMT
- Unfit: Chemo only
Prognosis
? not good
- Mean survival 3-5yrs
Thrombophilia
High platelets
Causes
1) Inherited
- Factor V Leiden (APC)
- Prothrombin gene mutation
- Antithrombin 3 deficiency
- Protein C and protein S deficiency
2) Acquired
- Anti-phospholipid syndrome
Presentation Recurrent embolisms - Arterial thrombosis - Venous thrombosis ETC
Investigations Thrombophilia screen - FBC, Clotting, fibrinogen leve;ls - FV leiden/APC resistance - Assays for AT, Protein C and protein S deficiency - Genertics - Electrophoresis - Lupus anticoagulant, anti-cardiolipin antibodies
Management
- Warfarin target INR 2-3, If recurs on warfarin target INR 3-4
- Don’t need lifelong anticoagulation if asymptomatic
- Rx acute thrombosis as per normal
Myelodysplastic syndrome
Cause
Investigations
Presentation
Management
Heterogenous group of conditions –> BM failure
Cause
Primary
Secondary: Chemo/radiotherapy
Investigations
Bone marrow tap: Hypercellular, blasts, ringed sideroblasts
FIlm: Peglet huer anomaly, blasts
Pancytopaenia
Presentation
No splenomegaly
Infections, Anaemia, Bleeding/Bruising
Management
Supportive: Transfusions, EPO, G-CSF
Immunosuppression
BM Transplant
Hodgkins lymphoma
Presentation
Epidemiology
Investigations
Management
Presentation
- Painless asymmetric lymphadenopathy, pain on alcohol, spreads contiguously from node to node
- EBV associated
- Cervical lymph nodes in 70%
- B symptoms
- Hepatosplenomegaly
Epidemiology
- YA and elderly = bimodal
Investigations
- LN biopsy: Reed stein berg cells
- CT/MRI CAP: Ann Arbor staging - remember B symptoms
Management
- ABVD
- BMT for relapse
HUS
Cause
E.coli
Presentation
- MAHA: Shcistocytes, low plateletss, normal clotting
- Thrombocytopaenia
- AKI
Management
- Supportive, resolves spontaneously; may need transfusion or dialysis
SCD
PP
Presentation
Investigations
Complications
Management
PP
Point mutation in beta globin gene glu–> val causes HbS vs HbA
HbS - prone to sickling when deoxygenated
–> thrombosis by occluding microvasculature
–> haemolysis as reduced life span
HbSS = SCA, HbSA = trait
Investigations:
Blood film
Hb electrophoresis
Triggers: Cold, infection, stress, hypoxic, dehydration
Presentation: SICKLED Splenomegaly may --> sequestration crises Infarctions - spleen Crises: Pulmonary, mesenteric - (vaso-occlusive, sequestration, aplastic) Kidney disease Liver, Lung disease ERECTION Dactylitis
Complications Aplastic anaemia --> parvovirus B19 Infections --> osteomyelitis Gallstones (DUH) Splenic sequestration Splenic infarction
Management
Chronic: Folate, Immunisations
Crises: Analgesia (opioids), oxygen, exchange transfusion, Abx e.g. ceftriaxone if necessary
Vascular/ platelets disorder vs coagulation disorder features
Vascular disorders/Platelet disorders
– bleeding into skin
– Bleeding mucus membranes, immediate, prolonged bleeding from cut
Coagulation disorder
– Deep bleeding: muscles, joints, tissues
– Delayed but severe bleeding after injury
Polycythaemia vera
Features
Investigations
Management
Prognosis
99% JAK2 +ve
Features Hyperviscosity - Headache, tinnitus, flushing Histamine release - Aquagenic pruritus - Splenomegaly - Hepatomegaly
Investigations -
High Hb, High Hct
JAK2
Management
- Aspirin aim for Hct <0.45
- Venesection if needed/young; Hydroxycarbamide if older/highrisl
Prognosis
30% –> MF
5% –> AML
Tumour lysis syndrome
Electrolyte abnormalities
hyperkalaemia hyperphosphataemia hyperuricaemia hypocalcaemia acute renal failure
G6PD deficiency
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red blood cell enzyme defect. It is more common in people from the Mediterranean and Africa and is inherited in an X-linked recessive fashion. Many drugs can precipitate a crisis as well as infections and broad (fava) beans
Pathophysiology
↓ G6PD → ↓ glutathione → increased red cell susceptibility to oxidative stress
Features neonatal jaundice is often seen intravascular haemolysis gallstones are common splenomegaly may be present Heinz bodies on blood films. Bite and blister cells may also be seen
Diagnosis is made by using a G6PD enzyme assay
Some drugs causing haemolysis
anti-malarials: primaquine
ciprofloxacin
sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas
Some drugs thought to be safe penicillins cephalosporins macrolides tetracyclines trimethoprim
AIHA
Autoimmune haemolytic anaemia (AIHA) may be divided in to ‘warm’ and ‘cold’ types, according to at what temperature the antibodies best cause haemolysis. It is most commonly idiopathic but may be secondary to a lymphoproliferative disorder, infection or drugs. AIHA is characterised by a positive direct antiglobulin test (Coombs’ test)
Warm AIHA
In warm AIHA the antibody (usually IgG) causes haemolysis best at body temperature and haemolysis tends to occur in extravascular sites, for example the spleen. Management options include steroids, immunosuppression and splenectomy
Causes of warm AIHA
autoimmune disease: e.g. systemic lupus erythematosus*
neoplasia: e.g. lymphoma, CLL
drugs: e.g. methyldopa
Cold AIHA
The antibody in cold AIHA is usually IgM and causes haemolysis best at 4 deg C. Haemolysis is mediated by complement and is more commonly intravascular. Features may include symptoms of Raynaud’s and acrocynaosis. Patients respond less well to steroids
Causes of cold AIHA
neoplasia: e.g. lymphoma
infections: e.g. mycoplasma, EBV
What is Waldenstrom’s macroglobulinaemia
Features
Waldenstrom’s macroglobulinaemia is an uncommon condition seen in older men. It is a lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein
Features monoclonal IgM paraproteinaemia systemic upset: weight loss, lethargy hyperviscosity syndrome e.g. visual disturbance the pentameric configuration of IgM increases serum viscosity hepatosplenomegaly lymphadenopathy cryoglobulinaemia e.g. Raynaud's
Dabigatran
MOA
Reversal
Excretion
Dabigatran is a new oral anticoagulant, used in this case to prevent another venous thromboembolic episode.
Dabigatran is a direct thrombin inhibitor.
Unlike other NOACs, dabigatran has an antidote i.e. Idarucizumab. Idarucizumab is a humanised monoclonal antibody that directly inhibits dabigatran.
Excretion = renal
Cryoprecipitate
Composition
Use
Composition Factor VIII 100IU Fibrinogen 250mg von Willebrand factor Variable Factor XIII Variable
Use
Blood product made from plasma
Usually transfused as 6 unit pool
Indications include massive haemorrhage and uncontrolled bleeding due to haemophilia
Neutropenic sepsis
Dx
Prophylaxis
Management
Neutropenic sepsis is a relatively common complication of cancer therapy, usually as a consequence of chemotherapy. It most commonly occurs 7-14 days after chemotherapy. It may be defined as a neutrophil count of < 0.5 * 109 in a patient who is having anticancer treatment and has one of the following:
a temperature higher than 38ºC or
other signs or symptoms consistent with clinically significant sepsis
Prophylaxis
if it is anticipated that patients are likely to have a neutrophil count of < 0.5 * 109 as a consequence of their treatment they should be offered a fluoroquinolone
Management
antibiotics must be started immediately, do not wait for the WBC
NICE recommend starting empirical antibiotic therapy with piperacillin with tazobactam (Tazocin) immediately
many units add vancomycin if the patient has central venous access but NICE do not support this approach
following this initial treatment patients are usually assessed by a specialist and risk-stratified to see if they may be able to have outpatient treatment
if patients are still febrile and unwell after 48 hours an alternative antibiotic such as meropenem is often prescribed +/- vancomycin
if patients are not responding after 4-6 days the Christie guidelines suggest ordering investigations for fungal infections (e.g. HRCT), rather than just starting therapy antifungal therapy blindly
there may be a role for G-CSF in selected patients
Negative prognostic features for Hodgkins Lymphoma
The presence of B symptoms (night sweats, weight loss and fever)
Male gender
Being aged >45 years old at diagnosis
High WCC, low Hb, high ESR or low blood albumin
Sickle cell anaemia mangement
Crisis management
analgesia e.g. opiates
rehydrate
oxygen
consider antibiotics if evidence of infection
blood transfusion
exchange transfusion: e.g. if neurological complications
Longer-term management
hydroxyurea
increases the HbF levels and is used in the prophylactic management of sickle cell anaemia to prevent painful episodes
NICE CKS suggest that sickle cell patients should receive the pneumococcal polysaccharide vaccine every 5 years
CLL Complication
Complications
anaemia
hypogammaglobulinaemia leading to recurrent infections
warm autoimmune haemolytic anaemia in 10-15% of patients
transformation to high-grade lymphoma (Richter’s transformation)
Richter’s transformation
Ritcher’s transformation occurs when leukaemia cells enter the lymph node and change into a high-grade, fast-growing non-Hodgkin’s lymphoma. Patients often become unwell very suddenly.
Ritcher's transformation is indicated by one of the following symptoms: lymph node swelling fever without infection weight loss night sweats nausea abdominal pain
Blood cell transfusion threshold
Patients without ACS Patients with ACS
Transfusion threshold 70 g/L 80 g/L
Target after transfusion 70-90 g/L 80-100 g/L
Platelet transfusion criteria
Active bleeding
Offer platelet transfusions to patients with a platelet count of <30 x 10 9 with clinically significant bleeding (World Health organisation bleeding grade 2- e.g. haematemesis, melaena, prolonged epistaxis)
Platelet thresholds for transfusion are higher (maximum < 100 x 10 9) for patients with severe bleeding (World Health organisation bleeding grades 3&4), or bleeding at critical sites, such as the CNS.
It should be noted that platelet transfusions have the highest risk of bacterial contamination compared to other types of blood product.
Pre-invasive procedure (prophylactic)
Platelet transfusion for thrombocytopenia before surgery/ an invasive procedure. Aim for plt levels of:
> 50×109/L for most patients
50-75×109/L if high risk of bleeding
>100×109/L if surgery at critical site
If no active bleeding or planned invasive procedure
A threshold of 10 x 109 except where platelet transfusion is contradindicated or there are alternative treatments for their condition
For example, do not perform platelet transfusion for any of the following conditions: Chronic bone marrow failure Autoimmune thrombocytopenia Heparin-induced thrombocytopenia, or Thrombotic thrombocytopenic purpura.
