Phase 2a Alex Cross and Jess Oscroft The Peer Teaching Society is not liable for false or misleading...

transcript

Phase 2a

Alex Cross and Jess Oscroft

The Peer Teaching Society is not liable for false or misleading information…

Haematology

• Anaemia (iron-deficiency anaemia, pernicious anaemia, folate-deficiency, normocytic anaemia, haemolytic anaemia, bone marrow failure, sickle cell anaemia, thalassaemia, glucose-6-phosphate deficiency)

• Polycythaemia• Deep vein thrombosis and thromboembolism• Bleeding (over-anticoagulation, disseminated intravascular

coagulation, platelet disorders e.g. ITP, TTP)• Leukaemia• Lymphoma• Myeloma• Infection (e.g. malaria)

Contents

• Haematology revision (unlike blood itself) is DRY

Introduction

FBCHaemoglobin 13-18g/dL in men

11.5-16.5g/dL women

MCV (Mean corpuscular volume)

75-95 fL

MCHC(Mean corp hb conc)

32-36 g/dL

Haematocrit(= % rbcs in blood)

0.4-0.52 in men0.36-0.47 in women

Red cell count 4.5 -6.5 x10^12 in men3.8-5.8 in women

Red cell distribution width(Range of cell size)

• ↓ number of red blood cells• or ↓ haemoglobin or ↓ haematocrit

• <13g/dL for men and <12 for women• Symptoms and signs?

Anaemia

AnaemiaMicrocytic Normocytic Macrocytic

Small red blood cells

MCV <80 fL

Large red blood cells

MCV >100 fL

Due to ↓ Hb production

Due to ↓ synthesis of red blood cells

Iron deficiency Bleeding ↓ folate or B12

Thalassaemia Combined iron, B12 and folate deficiency

Alcohol

SIderoblastic anaemia

Sickle cell disease Pernicious anaemia

Anaemia of chronic disease

Haemolytic anaemia

Aplastic anaemia Aplastic anaemia

• Cause- poor iron intake or blood loss• Sx- Koilonychia, angular chelitis, glossitis• Ix- • FBC (hypochromic, microcytic anaemia)• Serum ferritin < 15mcg/L• ?GI- endoscopy, coeliac

• Tx- Iron salt supplements, diet• Check response after 2-4 w (>2g/dL), • Continue for 3/12 after iron levels are normal

Iron deficiency anaemia

• Absorption of vit B12 in terminal ileum, needs intrinsic factor from gastric parietal cells

• Autoimmune • Sx of anaemia + paraesthesia, numbness (legs>

hands), cognitive changes, altered vision • Ix- FBC, blood film (Howell- Jolly), autoantibodies• Tx- IM hydroxocobalamin

Pernicious anaemia

• Cause- Malabsorption, • alcoholism, • malnutrition, • ↑ requirements

• Sx- Glossitis, mild peripheral neuropathy, depression

• Tx- 5mg Folic acid OD for 4/12

Folate deficiency anaemia

• Bone marrow can’t compensate for ↑ loss of RBCs• Intravascular (TTP, DIC, G6PD def, immune, trauma)• Extravascular (RBCs removed from blood)• Ix- Coombs’ test (Antibodies on RBCs)• Rx- Treat cause• Folic acid• Splenectomy

Haemolytic anaemia

• Seen in chronic infection, inflammation or cancer• ↓ EPO due to ↑ IL-1 and TNF• → ↑ IL-6 → ↑ Hepcidin from liver → ↓

ferroportin → ↓ iron available in circulation• Tx- Treat cause

Anaemia of chronic disease

• ↑ red blood cells (Hb >18.5g/dL), ↑ packed cell volume, ↑ haematocrit

• Causes: myeloproliferation• High altitude, hypoxia, cancer

• P/C- Tired, thrombosis, headaches, dizzy, pruritus worse after hot shower, splenomegaly, ↑ BP

• Ix- FBC, bone marrow and aspirate• Tx- Phlebotomy, aspirin, ?chemo

Polycythaemia

• A venous thrombus is a blood clot in a vein.

• Thrombosis = blood clot in a blood vessel.

• Most common type is DVT.• When a clot breaks loose and

travels in the blood = venous thromboembolism (VTE) —> Risk of PE!

• Clots in veins, can occur in any vein, more common in legs or pelvis.

• DANGEROUS - can embolise, break off and head up to the lungs = Pulmonary Emboli (PE)!!

• DVT’s occur in 25-50% of surgical patients, 65% of DVT’s are below the knee and are asymptomatic which rarely embolise to the lung.

• Risk factors - Age↑, pregnancy, malignancy, trauma, past DVT, obesity, immobility, infection, varicose veins, thrombophilia, HRT.

Deep Vein Thrombosis (DVT)

• Clinical Features - pain/ache, swelling, calf warmth, pitting oedema, erythema, Homan’s sign (pain in dorsiflexion).

• Diagnosis - D-Dimer (not specific!), Wells score, USS.

• Management - LMWH (enoxaparin), Warfarin with LMWH, stop LMWH when INR 2-3. Treat 3 months post op.

• Inferior vena cava filters can be used if active bleeding or anticoagulants fail to minimise PE risk.

Blood cell lineage

• 4 types: • Acute Myeloid (AML), 🌟

• Chronic myeloid (CML), • Acute lymphoblastic (ALL),

• Chronic lymphocytic (CLL)The Peer Teaching Society is not liable for false or misleading information…

Leukaemia

• Most common type of adult leukaemia• Cancer of myeloblasts • Cause- Genetics, radiation, chemo, Down’s• P/C- Bone marrow failure or organ infiltration• Ix- Bloods, bone marrow aspirate• Tx- Chemo in 2 phases: induction and post-

remission

• Myeloproliferation of one or all cell lines (erythroid, platelet and myeloid)

• 3 phases- Chronic, accelerated, blastic• Philadelphia chromosome: t(9;22)• P/C- Incidental diagnosis when asymptomatic

or insidious, general Sx• Ix- FBC, blood smear, marrow aspirate & biopsy,

cytogenetics• Tx- Tyrosine kinase inhibitors (Imatinib)

• Cancer of lymphoid progenitor cells• Most common leukaemia in children (80%)• P/C- Fatigue and malaise, bone marrow failure• IX- FBC, blood film, bone marrow aspirate &

biopsy • Tx- Chemo-

• remission induction, consolidation, maintenance

• Cancer of B lymphocytes → ↑ abnormal lymphocytes

• Dx- >5000 B cells/ mcL >3/12• Sx- 90% asymtpomatic, symmetrically enlarged

lymph nodes, BM failure• Tx- No cure

• Chemo prolongs survival• Splenectomy

• Cancer of lymphatic tissue• Types- Hodgkins, non-Hodgkins (90%)• RF- Genetics, viruses, environment• P/C- painless lymphadenopathy, B symptoms,

hepatosplenomegaly• Ix- Pancytopenia, CXR, LN biopsy, CT• Staging- Ann Arbor staging- I to IV• Tx- Rituximab and CHOP chemo• Vaccines

Lymphoma

• Histologically- Reed Sternberg cells• Assoc with EBV, HIV, smoking• Peaks 20-34 and 70• Sx- Same as previously • + alcohol induced pain• Mediastinal masses (→ dyspnoea, cough)

• Tx- Radiation, chemo (ABVD regime)

Lymphoma (Hodgkin’s)

• Malignant proliferation of plasma cells → ↑ paraprotein (IgG)

• Diffuse bone marrow infiltration bone → destruction & bone marrow failure

• Imbalanced bone remodelling (↑ osteoclast, ↓ osteoblast) → osteolysis and hypercalcaemia.

• Affects people >70

Myeloma (Pathophys)

Bone• Back pain• Fractures• Nerve compression• Hypercalcaemia

Myeloma (presentation)

• AKI• Dehydration

Blood• Lethargy• Bleeding• Bruising• Dizzy• Confusion• Blurred vis• Headaches• Infections

• Bloods (FBC, ESR, U&E, creatinine, Ca, albumin, uric acid)

• Serum and urine protein electrophoresis: Bence Jones in urine

• Immunoglobulin levels (one will be ↑, others may be ↓)

• Plain X-ray• Bone marrow aspirate

Myeloma (Ix)

• Incurable disease• <65y- Bortezomib, dexamethasone and

thalidomide• then autologous stem cell transplantation

• >65y where transplant isn’t appropriate• melphalan, prednisolone and thalidomide/

bortezomib

Myeloma (Tx)

• After injury - 3 processes halt bleeding: vasoconstriction, gap-plugging by platelets and the coagulation cascade.

• Vascular and platelet disorders lead into prolonged bleeding from cuts, bleeding into the skin and bleeding from mucous membranes.

• Coagulation disorders cause delayed bleeding into joints and muscles.

Bleeding Disorders

• Causes:

• Decreased marrow production - aplastic anaemia, megaloblastic anaemia.

• Marrow infiltration - leukaemia, myeloma.

• Marrow supression

• Excessive marrow destruction - ITP, TTP.

Platelet Disorders

• Immune thrombocytopenic purpura. (used to be called idiopathic)

• Autoimmune disease affecting platelets, number of circulating platelets is reduced as normal platelets are destroyed.

• Can be primary or secondary (SLE, APS, viral infections, heliobacter pylori, medication, lymphoproliferative disorders).

• Can occur in adults and children.

• Acute or chronic.

• Clinical Features - classic clinical picture is asymptomatic! Can present with petechiae and bruising, epistaxis, menorrhagia.

• Diagnosis - FBC, peripheral blood smear, bone marrow examination.

• Increase of megakaryocytes in marrow, anti platelet antibodies often present.

• Management - None if mild!

• If platelets <20x10^9/L - Prednisalone

• If relapse - splenectomy (cures 80%)

• Thrombotic Thrombocytopenic Purpura

• Deficiency in von Willebrand factor cleaving protein = ADAMTS1

• Congenital or acquired

• Causes - often unknown, drugs (clopidogrel, ciclosporin, rifampicin), pregnancy, HIV, SLE.

• Pathophysiology - deficiency of ADAMTS1 that cleaves VWF from multimers, so VWF builds up causing platelet aggregates to form and fibrin deposits in small vessels leaving to micro thrombi!

• Hess test - test of platelet adhesion and aggregation.

• Characterised by (5 things): Fever, fluctuating CNS signs (seizures, hemiparesis, reduced consciousness, reduced vision), microangipathic haemolysis, thrombocytopenia (reduced platelets), renal dysfunction (renal failure, haematuria, proteinuria).

• Diagnosis - Blood film (fragmented erythrocytes a.k.a schistocytes), FBC (platelets↓, Hb↓), renal functions tests.

• Management - URGENT IV plasma exchange may be life saving. Rituximab with steroids on admission, and splenectomy if relapse.

• ACUTE TEMP TP - often follows resp viral infection! Prednisalone, 85% of children recover within 1 year. Hess test +ve!!

• Causes:

• Congenital (haemophilia, VW disease),

• Acquired (anticoagulants, liver disease, Vit K deficiency)

• Remember the coagulation cascade! Extrinsic = tissue factor and intrinsic = contact activation.

Coagulation Disorders

Haemophilia• Type A =

Factor VIII deficiency

• Type B = Factor IX deficiency

• X-linked recessive pattern.

• Clinical Features depends on the severity.

• Diagnosis - APTT↓, factor VIII assay or factor XI assay ↓, Hb↓ if recent bleed.

• Management - avoid NSAIDs and IM injections.

• Minor bleeds - elevate and pressure

• Major bleeds - Increase factor VIII or XI levels to 50% of norm with transfusions!

• Children with severe haemophilia should receive prophylactic infusions (once-weekly or more frequently, ideally three times a week if venous access allows) of factor VIII to prevent haemarthroses and other bleeding episodes.

Haemophilia

• Disseminated Intravascular Coagulation (DIC)

• The coagulation mechanism (usually thrombin) is activated inappropriately and in a diffuse way.

• This can lead to thrombosis in the subacute or chronic form, but usually leads to haemorrhage as clotting factors are exhausted.

• Characterised by both thrombin and plasmin activation.

• Secondary complication of many diseases.

• Risk Factors - infections, malignancy (leukaemias), major trauma, APS, complications of pregnancy (HELLP syndrome, pre-eclampsia), incompatible blood transfusion, dissecting aortic aneurysm.

• Clinical Features - Bleeding from at least 3 unrelated areas, confusion, fever, ARDS, haemorrhage, purpura.

• Diagnosis - PT↑, APTT↑, platelets↓, fibrinogen↓. D-dimer, fibrin degradation products,

• Management - TREAT UNDERLYING CONDITION. Correct coagulation deficiencies - platelet transfusion, plasma exchange, heparin (in critically ill non-bleeding pt).

• Check for it if any sick patient from an endemic area!

• Species - P.vivax, P.ovale, P.malariae, P.falciparum, P.knowlesi.

• Plasmodium protozoa injected by female mosquitoes causes multiply RBCs - leading to haemolysis, RBC proliferation and cytokine release.

Infection - Malaria

• Clinical Features - Flu like symptoms (headache, malaise, myalgia, anorexia), fever like symptoms (rigors, syncope), anaemia, jaundice, hepatosplenomegaly.

• Diagnosis - Thick + thin blood films with Giemsa stain (gold standard) - Trophozoites. Rapid stick test available in 3rd world countries. FBC, U+E, LFT, BM.

• Management - Chloroquine (1st line in P.ovale and P.malariae). If resistant try quinine, or malarone. (For p.vivax use primaquine). P. falciparum —> admit to hospital, oral quinine sulphate 5-7 days and doxycycline 7 days, malarone for 3 days, Riamet 4 tablets stat.

• Prophylaxis - Mosquito nets, doxycycline.

Malaria

Questions?

Phase 2a Alex Cross and Jess Oscroft The Peer Teaching Society is not liable for false or misleading...

Documents