Phase 2a Haem Disease Flashcards
Iron deficiency Anaemia(symptoms)
(RF)
Pathology
Symptoms
Investigations
Treatment
Commonly caused by PICA (eating dirt/soil - or any non food items, sucking thumb)
- Most common type of anaemia
- Causes Microcytic Hypochromic anaemia
- Iron is required for haemoglobin synthesis
RF - Pregnancy, vegan diet, menorrhagia
Path - caused by:
- decreased dietary iron intake
- reduced iron absorption (e.g. coeliac disease)
- Increased iron requirements (e.g. pregnant)
- Increased iron loss through bleeding (e.g. menorrhagia, GI bleeding)
Symptoms
- Fatigue, exertional dyspnoea, koilonychia (spooning/thinning of nails), glossitis and difficulty swallowing (inflammation of tongue- difficulty swallowing), angular stomatitis (cracked sores in the corners of mouth),
- PICA - chewing things with no nutritional value
Investigations
1st - Iron studies –> Decreased serum Fe, decreased ferritin, decreased transferrin saturation, increased TIBC
TIBC - total iron binding capacity - space for iron to attach on transferrin molecules
- Transferrin saturation - proportion of transferrin molecules bound to iron.
–> Peripheral blood smear (microcytic, hypochromic RBC)
Treatment
1st - Oral iron replacement - ferrous sulphate. If FS poorly tolerated then ferrous gluconate
- IV iron replacement
Thalassemia (symptoms)
(RF)
Pathology
Symptoms
Investigations
Treatment
- Autosomal recessive haemoglobinopathy (genetic defect in protein chains) - leading to RBC becoming more fragile - resulting in haemolytic anaemia
- Prevalent where malaria is (middle east, north africa, SE asia, india)
PATH
Alpha thalassemia (less common) - Decreased/absent production of at least 1 of the 4 alpha globin genes that make 1 alpha chain. (Excess unmatched beta globin chains aggregate and damage RBCs - haemolytic anaemia
Beta thalassemia - mutation of beta globin gene (2 genes make 1 beta chain) - excess alpha chains precipitate in erythroid precursors causing ineffective erythropoiesis.
– Can only manifest after transition from fetal Hb to adult Hb as HbF does not have beta chains. 2 beta globin genes either defective/missing = beta thalassemia major = transfusion dependent thalassemia)
Symptoms
Alpha/beta thal minor - Fatigue, pallor, exertional dyspnoea, chest pain (general anaemia)
Beta thal major -
General anaemic symptoms plus
Over time: CHIPMUNK FACIES (enlarged forehead and cheekbones), misaligned teeth, hepatosplenomegaly
Investigations
1st - FBC + peripheral blood smear (microcytic anaemia, hypochromic RBC, increased reticulocyte, tear drops (BM not producing normal RBC)
GS - Haemoglobin electrophoresis (diagnose globin abnormalities)
X-ray of skull - hair on end appearance (increased BM activity)
Treatment
Alpha - Folate supplements + blood transfusion
Beta
1st - Regular blood transfusion + iron monitoring + iron chelation therapy (desferrioxamine)
- Splenectomy - if massively enlarged and at risk of rupture
- Folate supplements (for haemolytic anaemia)
Definitive - BM stem cell transplant
Sickle cell anaemia (investigation and treatment)
(RF)
Pathology
Symptoms
Investigations
Treatment
- Autosomal recessive haemoglobinopathy resulting in the production of sickle cell haemoglobin
- Normocytic anaemia
- Common in Africa due to antimalaria properties
PATH
Glutamic acid (GAG) –> Valine (GTG) at 6th amino acid of the beta globin chain. Causes HbS.
Results in:
- Vaso-occlusion in small vessels, slowing blood flow (in long bone)
- Splenic sequestration - sickle cells block blood vessels leading out of spleen
- Acute chest crises - when vessels supplying lungs become clogged
(Also deformed cells have a smaller lifespan and are prone to haemolysis)
SYMPTOMS
Fatigue, tachypnoea, jaundice (due to haemolysis), visual floaters (occlusion of retinal arterioles), bone pain (vaso-occlusion)
INVESTIGATIONS
(For newborns - heel prick test)
1st FBC + peripheral blood smear - Normocytic, normochromic with increased reticulocytes. + sickled RBC and Howell Jolly bodies (RBC with DNA indicate hyposplenism)
GS - Hb electrophoresis - diagnostic with proportion of HbS 75-90%
TREATMENT
- For acute complications e.g. Acute chest crisis - analgesia + oxygen.
- If infection e.g. parvovirus B19 - aplastic anaemia give antibiotics
LONG TERM
- HYDROXICARBAMIDE (increases HbF)
- Blood transfusion + iron chelation
Last resort - BM stem cell transplant
What chains make up HbF and HbA
HbF - 2 alpha + 2 gamma chains
HbA - 2 alpha + 2 beta chains
G6PD deficiency
(RF)
Pathology
Symptoms
Investigations
Treatment
- Inherited X linked enzyme deficiency
- Common in Africa, asia, middle east (malaria)
RF - Males, neonates, ethnicity, family history
PATH
- G6PD is required by cells for protection against ROS
- G6PD deficiency makes cells more vulnerable to ROS, leading to haemolysis of RBC
SYMPTOMS
Mostly asymptomatic but can present with:
- Jaundice (haemolytic anaemia)
- Pallor (anaemia)
INVESTIGATIONS
1st line - FBC + blood smear/film - Normocytic, normochromic RBC, increased reticulocytes. + HEINZ bodies (indicate oxidative injury to erythrocytes - denatured haemoglobin)
GS - decreased serum G6PD levels
TREATMENT
1st - Avoid precipitants e.g. Fava beans and certain medication (nitrofurantoin, trimethoprim)
- Blood transfusion if rapid anaemia and jaundice
Autoimmune haemolytic anaemia (treatment)
(RF)
Pathology
Symptoms
Investigations
Treatment
- Premature destruction of RBCs
- Normocytic
RF - autoimmune disorders
PATH
Antibodies (cold agglutinins produced by B lymphocytes) bind to the surface of RBC, resulting in increased destruction by macrophages in the spleen. (cold HA)
(Warm HA - typically idiopathic but more common - IgG antibodies trigger destruction of RBC in the spleen, occurs at body temperature)
SYMPTOMS
Fatigue, dyspnoea, pallor, jaundice, splenomegaly
INVESTIGATIONS
- Direct antigloublin test (COOMBS) - positive suggests antibody bound to patient’s own cells. (Negative - hereditary spherocytosis - spectrin membrane protein deficiency)
Bite cells?
TREATMENT
- Blood transfusion (iron chelation therapy)
- Prednisolone - corticosteroid that reduces antibody production
- Rituximab - targets CD20 on B lymphocytes (decreasing antibody production)
Give examples of megaloblastic and non megaloblastic anaemia
Megaloblastic - Vitamin B12 deficiency, folate deficiency (neutrophils have >6 lobes)
Non-megaloblastic -
Alcohol - toxic to RBC (can deplete folate)
Hypothyroidism - interferes with erythropoietin (T3/4 helps stimulate production of erythropoietin)
Liver disease - decreased production of erythropoietin and decreases iron metabolism (e.g. storage and release)
Folate deficiency anaemia
(RF)
Pathology
Symptoms
Investigations
Treatment
(Vitamin B9)
- Macrocytic, megaloblastic
PATHOLOGY
- Found in green vegetables, legumes and fruits (Synthetic form - folic acid)
Deficiency due to
- Excessive cooking - destroys folate
- Poor dietary intake
- Malabsorption (coeliac/crohn’s)
- Pregnancy
Medications - Trimethoprim, methotrexate
Folate required for DNA replication
SYMPTOMS
- Fatigue, dyspnoea, pallor, angular stomatitis, glossitis (no neuro symptoms like B12)
INVESTIGATIONS
FBC + blood smear - Macrocytic, megaloblasts
Serum Folate - low
(Possible concomitant B12 deficiency)
TREATMENT
1st - Dietary advice then oral folic acid replacement
If concomitant B12 deficiency - replace B12 first
HIV
(RF)
Pathology
Symptoms
Investigations
Treatment
HIV 1 - most common, virulent
HIV 2 - more common in West Africa less virulent
RF - IV drug users, sex workers, unprotected intercourse
PATH
HIV glycoprotein 120 binds to CD4 receptors on T cells –> Fusion of viral membrane with cell membrane via glycoprotein 41 –> endocytosis of viral RNA, reverse transcriptase and integrase –> reverse transcriptase converts viral RNA to DNA –> integrase integrates viral DNA into host cell DNA –> HIV uses the host cell machinery to replicate/remains dormant –> virus uses host’s enzymes for protein synthesis and the newly formed virus (RNA + viral proteins synthesised) leaves the cell pushing through the membrane –> uses lipids of the cell to form GP 120 and 41 in the process. (Viral copies increase and CD4+ count decreases)
AIDS related illness can develop when CD4 count drops below 500 - (fever, diarrhoea, sweats, shingles, weight loss, oral candidiasis)
AIDS defining illness (CD4+ count <200) - CMV colitis, pneymocystis jirovecii pneumonia, kaposi’s sarcome, TB, lymphoma, candida albicans
INVESTIGATIONS
ELISA - enzyme linked immunosorbent assay –> positive for Anti HIV immunoglobulin and p24 antigen
Monitor progression - via HIV RNA copies and CD4+ count
TREATMENT
Highly active antiretroviral therapy (HAART)
3 drugs: Bictegravir (integrase inhibitor), emitricitabine, tenofovir alafenamide (both reverse transcriptase inhibitor)
+ prophylactic Co trimoxazole (for PCP)
Acute Myeloid Leukaemia (Just treatment and pathology)
(RF)
Pathology
Symptoms
Investigations
Treatment
- Haematological malignancy
- Proliferation of myeloid blasts in the bone marrow
RF - >65 years, prior chemo, previous haematological disorders (MDS, aplastic anaemia), radiation exposure
PATHOLOGY
ASSOCIATED WITH DIC
- Chromosomal Translocation - t(15:17)
- Associated with Down’s syndrome,
Due to risk factors + syndromes mentioned –> There is an accumulation of immature myeloid blasts unable to differentiate into mature neutrophils, RBC and platelets –> leads to Bone Marrow failure.
3 year survival - 20% if not treated asap
SYMPTOMS
- BM failure -
Anaemic symptoms (fatigue, dyspnoea, light headed, pallor)
Neutropenia symptoms (infection, fever)
Thrombocytopenia symptoms (bleeding gums, increased risk of bleeding, petechiae - non blanching rash)
INVESTIGATIONS
FBC + blood film - Pancytopenia, presence of myeloid blasts and AUER RODS (+ positive myeloperoxidase stain)
Diagnostic –> BM biopsy and aspirate - >10% infiltration by myeloid blasts
TREATMENT
Chemotherapy + All trans retinoic acid (vitamin A that helps with growth and development of cells)
(Allopurinol may be given to prevent tumour lysis syndrome)
Consider: Antibiotic prophylaxis for neutropenia/transfusions for anaemia
Last resort: BM transplant
What is tumour lysis syndrome?
Tumour lysis syndrome occurs due to chemicals released when cells are destroyed by chemotherapy. It results in:
High uric acid
Hyperkalemia (cardiac arrhythmias)
High phosphate
Hypocalcemia
Uric acid can form crystals in the interstitial space and tubules of kidneys causing acute kidney injury. (Uric acid nephropathy)
Good hydration and allopurinol can be used to suppress uric acid levels. (or treat TLS)
Chronic Myeloid Leukemia
(RF)
Pathology
Symptoms
Investigations
Treatment
Proliferation of myeloid progenitors (results in hyperplasia of bone marrow)
- 65-74 year males, exposure to radiation
PATHOLOGY
- Chromosomal translocation t(9.22) - PHILADELPHIA CHROMOSOME
- Fusion of genes result in tyrosine kinase being constitutively active –> uncontrolled proliferation of myeloid cells in BM
(As CML has slower onset than AML, there are mature forms of granulocytes present compared to maturation arrest in AML)
SYMPTOMS
(Also weight loss and night sweats - which wouldn’t be seen in AML)
- Pancytopenia symptoms
Anaemic symptoms (fatigue, dyspnoea, light headed, pallor)
Neutropenia symptoms (infection, fever)
Thrombocytopenia symptoms (bleeding gums, increased risk of bleeding, petechiae - non blanching rash)
+ HEPATOSPLENOMEGALY (weight loss, excess sweating)
INVESTIGATIONS
First line - Anaemia, thrombocytopenia but elevated granulocytes
DIAGNOSTIC - Philadelphia chromosome genetic test (9:22)
BM biopsy - elevated granulocytes
TREATMENT
Chemotherapy + IMATINIB (tyrosine kinase inhibitor)
(Possible allopurinol for TLS)
Chronic Lymphoid Leukaemia
-Treatment
(RF)
Pathology
Symptoms
Investigations
Treatment
- Neoplastic proliferation of lymphocytes (mostly B lymphocytes)
- Most common leukaemia
RF - >60, males, whites, family history
(Multifactorial causes)
- Slow proliferation of B lymphocytes that are mature but functionally impaired (can proliferate but unable to differentiate into plasma cells) –> these cells build up excessively and infiltrate organs (spleen, liver, BM) - interferes with blood cell production
(Can develop hypogammaglobulinemia - deficiency of immunoglobulins, increasing patient’s risk of infection and other diseases)
SYMPTOMS
- Lymphadenopathy, hepatosplenomegaly, dyspnoea + fatigue, bleeding
Investigations
1st FBC - Elevated WBC count (Anaemia, thrombocytopenia)
Blood film – smudge cells present (fragile lymphocytes)
GS - Immunophenotyping
Immunoglobulin levels - low, hypogammaglobulinemia (ordered for patients with recurrent infections)
Treatment
1st - Chemotherapy (with allopurinol)
IV immunoglobulin for treating hypogammaglobulinemia
(Radiotherapy, stem cell transplant)
What is an important complication of chronic lymphocytic leukaemia?
Richter transformation
B cells massively accumulate in lymph nodes resulting in massive lymphadenopathy. This can cause CLL which is usually indolent to transform into a high grade, aggressive non hodgkin’s lymphoma.
(sudden onset B symptoms - fever, night sweats)
Acute lymphoid leukaemia
(everything)
(RF)
Pathology
Symptoms
Investigations
Treatment
A malignancy that develops when a lymphoid progenitor cell becomes genetically altered and undergoes uncontrolled proliferation
RF - <5 years, genetics, family history of ALL
- Most common childhood malignancy
PATHOLOGY
- B lymphoid progenitor is involved in most cases (75% with T cell progenitor in 25%) – Bone marrow produces immature cells - develop into lymphoblasts
- Cytogenic abnormality T(12:21)
- Associated with Downs syndrome and radiation exposure
SYMPTOMS
- Anaemic symptoms (fatigue, dizziness, dyspnoea), petechiae, hepatosplenomegaly, enlarged lymph node
INVESTIGATIONS
1st FBC - Pancytopenia
Blood film - increased lymphoblasts
(Can get pancytopenia with lymphoblasts as lymphoblasts can crowd out normal haematopoietic stem cells - reduced RBC, WBC, platelets)
GS - BM biopsy and aspiration > 20% lymphoblasts
TREATMENT
Chemotherapy (possible allopurinol)
