Phase 2a Alex Cross and Jess Oscroft

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

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

3. Haematology revision (unlike blood itself) is DRY • Introduction • The Peer Teaching Society is not liable for false or misleading information…

4. FBC • The Peer Teaching Society is not liable for false or misleading information…

5. ↓ number of red blood cells or ↓ haemoglobin or ↓ haematocrit <13g/dL for men and <12 for women Symptoms and signs? • Anaemia • The Peer Teaching Society is not liable for false or misleading information…

6. Anaemia • The Peer Teaching Society is not liable for false or misleading information…

7. 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 3/12after iron levels are normal • Iron deficiency anaemia • The Peer Teaching Society is not liable for false or misleading information…

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

9. Cause- Malabsorption, alcoholism, malnutrition, ↑ requirements Sx- Glossitis, mild peripheral neuropathy, depression Tx- 5mg Folic acid OD for 4/12 • Folate deficiency anaemia • The Peer Teaching Society is not liable for false or misleading information…

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

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

12. ↑ 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 • The Peer Teaching Society is not liable for false or misleading information…

13. 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! • VTE • The Peer Teaching Society is not liable for false or misleading information…

14. 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) • The Peer Teaching Society is not liable for false or misleading information…

15. 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. • DVT • The Peer Teaching Society is not liable for false or misleading information…

16. Blood cell lineage • The Peer Teaching Society is not liable for false or misleading information…

17. 4 types: Acute Myeloid (AML), 🌟 Chronic myeloid (CML), Acute lymphoblastic (ALL), Chronic lymphocytic (CLL) • Leukaemia • The Peer Teaching Society is not liable for false or misleading information…

18. 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 • AML • The Peer Teaching Society is not liable for false or misleading information…

19. 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) • CML • The Peer Teaching Society is not liable for false or misleading information…

20. 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 • ALL • The Peer Teaching Society is not liable for false or misleading information…

21. 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 • CLL • The Peer Teaching Society is not liable for false or misleading information…

22. LOL • The Peer Teaching Society is not liable for false or misleading information…

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

24. 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) • The Peer Teaching Society is not liable for false or misleading information…

25. 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) • The Peer Teaching Society is not liable for false or misleading information…

26. Bone Back pain Fractures Nerve compression Hypercalcaemia • Myeloma (presentation) • Blood • Lethargy • Bleeding • Bruising • Dizzy • Confusion • Blurred vis • Headaches • Infections • AKI • Dehydration • The Peer Teaching Society is not liable for false or misleading information…

27. 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) • The Peer Teaching Society is not liable for false or misleading information…

28. 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) • The Peer Teaching Society is not liable for false or misleading information…

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

30. Causes: Decreased marrow production - aplastic anaemia, megaloblastic anaemia. Marrow infiltration - leukaemia, myeloma. Marrow supression Excessive marrow destruction - ITP, TTP. • Platelet Disorders • The Peer Teaching Society is not liable for false or misleading information…

31. 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. • ITP • The Peer Teaching Society is not liable for false or misleading information…

32. 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%) • ITP • The Peer Teaching Society is not liable for false or misleading information…

33. 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. • TTP • The Peer Teaching Society is not liable for false or misleading information…

34. 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!! • TTP • The Peer Teaching Society is not liable for false or misleading information…

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

36. Haemophilia • Type A = Factor VIII deficiency • Type B = Factor IX deficiency • X-linked recessive pattern. • The Peer Teaching Society is not liable for false or misleading information…

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

38. 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. • DIC • The Peer Teaching Society is not liable for false or misleading information…

39. 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). • DIC • The Peer Teaching Society is not liable for false or misleading information…

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

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

42. Questions? • The Peer Teaching Society is not liable for false or misleading information…