HAEMATOLOGY OF CHRONIC DISORDERS (1) copy.pptx

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1. HAEMATOLOGY OF CHRONIC DISORDERS GROUP 1

2. Group Members Akagha Akunna Angelica Akinsanya Oyinkansola Christine Akogwu Mercy Igbe Alomooluwa Oluwamayowa Hephzibah Aregbesola Diekolayomi Sarah Azubuike Victory Onyebuchi Dike-Israel Vanessa Chinonyelum Ebiowe Samuel Miracle Enaohwo Evelyn Ogheneruona Idowu Moyinoluwa Joan Ifeanyichukwu Ogeoma Chidinma Musa Tekomi Testimony Nwa Edidiong Hanson Nwajei Christopher-Lawrence Chidera Nwogoh Martin Ikechukwu Okafor Obinna Kingsley Okereke Princess Deborah Okorie Adaeze Alexandria Olatunji Jochebed Oluwaferanmi Onugha Jessica Chiamaka Oseni Oluwabusayo Esther Otis-Ehiemuan Osemudiamen Anthony Owolabi Hamida Adedolapo Oyelakin Oluwatosin Olaoluwa Oyewolu Oluwademilade Opemipo

3. SYSTEMIC DISEASES

4. Congestive Heart Failure A syndrome that can be caused by a variety of abnormalities, including pressure and volume overload, loss of muscle, primary muscle disease or excessive peripheral demands such as high output failure in both ventricles. The current worldwide prevalence of CHF is 63.34 million cases according to the Global Health Data Exchange registry. The registry also notes a predilection for race with a 25% higher prevalence of HF in patients of African-American descent than Caucasians.

5. Aetiology Coronary artery disease Myocardial infarction. Diabetes mellitus Hypertension Valvular heart disease Uncontrolled arrhythmias

6. Pathophysiology Several compensatory mechanisms kick in to maintain CO and meet systemic demand. These mechanisms may restore CO to near-normal. Their excessive response over the long-term become deleterious and cause worsening heart failure!

7. Haematological findings There is anemia is present in 30–50% of patients with CHF which is secondary to chronic kidney disease, diabetes and release of cytokines increasing hepcidin synthesis (reducing iron absorption and recycling of iron from macrophages) and reducing erythropoietin secretion. Peripheral blood film slide from a patient with CHF 2 to CKD

8. Treatment Oral or intravenous iron may improve left ventricular ejection fraction, lower CRP and brain natriutetic peptide (BNP) levels, reduce fatigue, and increase exercise capacity and quality of life, even in those without iron deficiency.

9. Crohn’s Disease Crohn’s disease is a chronic inflammatory disorder of the gastrointestinal tract characterized by local deposition of histiocytes and the development of non-caseating granulomas Crohn’s disease is more common North America and Europe, where it 20-30% of all diagnoses are made before age 20 years- however, a greater proportion its diagnoses have been made in the older population. It has little incidence among Africans

10. Pathophysiology It is implicated by the c hronic inflammation from T-cell activation leading to tissue injury. There is then an unrestrained response of type 1 helper cells after activation by an antigen, stimulating the inflammatory response and resulting in direct injury to the intestine. Extensive inflammation may result in hypertrophy of the muscularis mucosae, fibrosis, and stricture formation, which can lead to bowel obstruction.

11. Haematological findings T hrombocytosis and anaemia, resulting from functional or absolute iron deficiency, are common secondary changes in the disease. T here could be an increased platelet function, fibrinolytic abnormalities, hypercoagulation, recognised to be caused by inflammation, may lead to thromboembolic events. Reduced FXIII (Fibrin-stabilizing factors) levels have been observed in Crohn’s disease.

12. Peripheral blood film slide showing microcytic anaemia, a complication of Crohn’s disease

13. Management Iron supplementation as soon as a patient is found to have iron deficiency anaemia and in the form of oral iron, parenteral iron, or erythropoietin. Aspirin when platelet counts exceed 1,000,000/ μL Fresh frozen plasma or cryoprecipita te to treat bleeding Pain relief

14. Renal failure Renal failure or chronic renal failure of chronic kidney disease is the inability of the kidneys to perform excretory function leading to retention of nitrogenous waste products from the blood. CKD is a progressive condition that affects >10% of the general population worldwide, amounting to >800 million individuals. It is more prevalent in older individuals, women, racial minorities, and in people experiencing diabetes mellitus and hypertension.

15. Aetiology Diabetes Hypertension Polycystic kidney disease Glomerular disease

16. Haematological findings A nemia is a common finding in CKD . It is majorly due to insufficient erythropoietin. Anaemia could also result from chronic blood loss, hemolysis and bone marrow suppression by retained uremic factors. Reduced Hb levels Reduced platelet count Prolonged bleeding Increased WBC count

17. Management Investigations Urinalysis Dipstick for blood and protein; Microscopy for cells, casts, and crystals Renal ultrasound sonography (USS) Radionucleotide renal scan, CT scan, and/or MRI Kidney biopsy Treatment Dependent on the cause of failure. Treatment is made by replacing renal function through: Dialysis Kidney transplant

18. Systemic Lupus Erythematosus Systemic lupus erythematosus is a systemic autoimmune disease with a worldwide distribution. Although both men and women of all age groups can be affected, women outnumber men almost 10-fold and the typical lupus patient is a young woman during her reproductive years.

19. Pathophysiology SLE occurs through the production of auto-antibodies that attacks a person’s own cells thus contributing to the inflammation of various parts of the body, and may cause damage to organs and tissues.

20. Haematological Findings Haematological abnormalities in SLE can be caused by its pathophysiology or can be due to certain treatment options like immunosuppressive therapy. Anaemia resulting from renal impairment, drug-induced GI blood loss, or autoimmune haemolysis ( typically with IgG and the C 3 component of complement on the surface of the RBC). Leukopenia with reduced neutrophil and lymphocyte counts. Arterial and venous thrombosis.

21. Management Investigations Erythrocyte sedimentation rate Blood counts and differential blood counts Urinalysis Antinuclear antibodies (ANA) (Hep-2 cell test with fluorescence pattern) Treatment Topical glucocorticoids for skin lesions Antimalarials unless there are contraindications. Immunosuppression Adjunct treatment which is determined by the comorbidities such as infections, HTN, arteriosclerosis, diabetes, osteoporosis

22. Rheumatoid Arthritis Rheumatoid arthritis is a chronic inflammatory disease that results in joint destruction. It is characterised by severe pain, swelling, stiffness and loss of function of the joint. Its hallmark feature is polyarthritis (synovitis) affecting the hands and feet. The precise cause is not known but genetics, hormones, and environment are contributing factors. RA has a population prevalence of 0.5-1% annually depending on gender, race and calendar year.

23. Pathophysiology RA is an autoimmune disease characterised by dysregulation of the immune system resulting in chronic activation of T-cell responses and overproduction of proinflammatory cytokines (TNF and IL-1). The synovium becomes infiltrated with lymphocytes especially helper T cells, plasma cells, and macrophages. Inflammatory granulation tissue (pannus) spreads over and under the articular cartilage which is irreversibly eroded and destroyed.

24. Haematological findings Mild anaemia characterised by low concentration of serum iron and low serum iron binding capacity. Chronic anaemia in true iron deficiency secondary to gastrointestinal blood loss from those treated with NSAIDs White blood cells may be within normal range - slightly elevated or markedly elevated due to left-shift.

25. Peripheral blood film showing rheumatoid arthritis

26. Management Investigations Erythrocyte sedimentation rate C-reactive protein level Rheumatoid factor assay Antinuclear antibody assay Anti-cyclic citrullinated peptide and anti-mutated citrullinated vimentin assays Radiography of the joints MRI scans or primarily the cervical spine. Ultrasonography of joints, tendon sheaths. Joint aspiration and analysis of synovial fluid may be considered.

27. Treatment Non-pharmacological Exercise Diet Massage Counselling Stress reduction Physical therapy Surgery Pharmacological NSAIDs Immunosuppressants Non-biologic and biologic disease-modifying antirheumatic drugs (DMARDs)

28. Asthma Asthma is a major noncommunicable disease (NCD), affecting both children and adults, and is the most common chronic disease among children. Inflammation and narrowing of the small airways in the lungs cause asthma symptoms, which can be any combination of cough, wheeze, shortness of breath and chest tightness. Asthma affected an estimated 262 million people in 2019 (1) and caused 455 000 deaths.

29. Pathophysiology In the pathophysiology of Asthma, Airflow limitation in asthma is recurrent and caused by a variety of changes in the airway. These include: Bronchoconstriction.: In asthma, the dominant physiological event leading to clinical symptoms is airway narrowing and a subsequent interference with airflow. In acute exacerbations of asthma, bronchoconstriction occurs quickly to narrow the airways in response to exposure to a variety of stimuli including allergens or irritants. Allergen-induced acute bronchoconstriction results from an IgE-dependent release of mediators from mast cells that includes histamine, tryptase, leukotrienes, and prostaglandins that directly contract airway smooth muscle. Airway oedema : As the disease becomes more persistent and inflammation more progressive, other factors further limit airflow. These include oedema, inflammation, mucus hypersecretion and the formation of inspissated mucus plugs, as well as structural changes including hypertrophy and hyperplasia of the airway smooth muscle.

30. Pathophysiology continued Airway hyperresponsiveness: Airway hyperresponsiveness—an exaggerated bronchoconstrictor response to a wide variety of stimuli—is a major, but not necessarily unique, feature of asthma. The degree to which airway hyperresponsiveness can be defined by contractile responses to challenges with methacholine correlates with the clinical severity of asthma. Airway remodelling. Airway remodelling involves an activation of many of the structural cells, with consequent permanent changes in the airway that increase airflow obstruction and airway responsiveness and render the patient less responsive to therapy. These structural changes can include thickening of the sub-basement membrane, subepithelial fibrosis, airway smooth muscle hypertrophy and hyperplasia, blood vessel proliferation and dilation, and mucous gland hyperplasia and hypersecretion.

31. Haematological Findings Common hematological abnormalities encountered during asthma include: Increased eosinophil count (Eosinophilia) Increased neutrophil count (Neutrophilia) Leukocytosis Increased erythrocyte sedimentation rate

32. Management Management of persistent asthma requires: Avoidance of aggravating environmental factors Use of short-acting β2-agonists for rapid relief of symptoms Daily use of inhaled corticosteroids. Other controller medications, such as long-acting bronchodilators and biologics, may be required in moderate and severe asthma. Patients with severe asthma generally benefit from consultation with an asthma specialist for consideration of additional treatment, including injectable biologic agents.

33. BLOOD RELATED DISEASES

34. Chronic anaemia Anaemia is a condition in which the blood doesn’t have enough healthy red blood cells. Chronic anaemia or anaemia of chronic diseases occurs when an autoimmune disease or other illness lasts longer than 3 months and causes inflammation as well. This pathology affects the body’s ability to use iron needed to make enough RBCs. Chronic anaemia is the second most common form of anaemia worldwide.

35. Pathophysiology The pathophysiology of ACD is related to a reduction in the release of iron from the macrophages to the plasma because of raised serum hepcidin levels, reduced red blood cell span and inadequate erythropoietin response to the anaemia caused by the effects of cytokines such as IL-1 and TNF on erythropoietin.

36. Haematological findings Normochromic, normocytic or mildly hypertonic (MCV rarely <75Fl) Both serum iron and total iron-binding capacity are reduced. Serum ferritin is normal or raised. Bone marrow storage of iron is normal but erythroblast iron is reduced

37. Peripheral blood film showing ACD- basophilic stippling

38. Management Investigations Bone marrow biopsy to test for iron stores and serum iron levels Complete blood count Reticulocyte count C-reactive protein Erythrocyte sedimentation rate Treatment Successful treatment of underlying disease Erythropoietin injections improve the anaemia. Do not administer iron!

39. Haemophilia Haemophilia is an inherited bleeding disorder characterized by the inability of the blood to clot properly. There are three types of haemophilia: Haemophilia A, B and C. Haemophilia A: is a recessive X-linked genetic disorder involving a lack of clotting factor VIII. It is the most common type of haemophilia, representing about 80% of all haemophilia cases. Haemophilia B: is a recessive X-linked disorder involving a lack of clotting factor IX. Represent about 20% of all haemophilia cases. Haemophilia C: is an autosomal disorder involving a lack of clotting factor XI. It is the rarest form of haemophilia.

40. Epidemiology Haemophilia A affects about 1 in 5,000-10,000. Haemophilia B affects about 1 in 40,000 males. Haemophilia C affects about 1 in 100,000 and is common in Ashkenazi and Iraqi jews. In Nigeria, there is an estimated 9,000-12,000 people living with haemophilia according to World federation of Haemophilia (WFH). Haemophilia is more common in males than in females because the affected genes are located on the X chromosome. Females are usually carriers, but can be affected in rare cases where both X chromosomes are affected.

41. Pathophysiology Haemophilia is caused by a mutation or change in one of the genes that provides instructions for synthesis of the clotting factor proteins needed to form a blood clot. These genes are located on the X chromosome. This change or mutation can cause abnormal or deficient function of the clotting proteins or an overall deficiency of the clotting proteins themselves.

42. Pathophysiology continued In haemophilia A, the factor VIII gene is affected, in haemophilia B, there is a decrease in the clotting activity of factor IX, while in haemophilia C, the factor XI gene is affected. When any of these factors are deficient of dysfunctional, the intrinsic pathway of the coagulation cascade cannot be appropriately activated, thus making the process of clot formation deficient, resulting in prolonged bleeding.

43. Clinical Manifestations Unexplained or excessive haemorrhage from injuries. Cephalohematomas in new-borns during delivery. Haematuria and bloody stool. Hemarthrosis Excessive formation of subcutaneous hematomas. Muscle haemorrhages and hematomas Idiopathic epistaxis Prolonged haemorrhage after surgical or dental procedures. Prolonged post circumcision haemorrhage.

44. Haematological Findings HAEMOPHILIAS CLOTTING FACTORS BLEEDING TIME PROTHROMBIN TIME APTT FIBRINOGEN PLATELET COUNT FACTOR VIII FACTOR IX FACTOR XI A Low Normal Normal Normal Normal Prolonged Normal Normal B Normal Low Normal Normal Normal Prolonged Normal Normal C Normal Normal Low Normal Normal Prolonged Normal Normal

45. Management Investigations Full/Complete Blood Count (including platelet count) Activated Partial Prothrombin Time Bleeding time Prothrombin time Fibrinogen test Coagulation Factor Assays Factor VIII: Low in A but normal in B and C. Factor IX: Low in B but normal in A and C. Factor XI: Low in C but normal in A and B. Treatment The main treatment for severe haemophilia involves replacing the clotting factors needed via IV infusion of donated blood or free recombinant clotting factors. Other treatments include: Desmopressin Antifibrinolytic drugs Fibrin sealants Emicizumab (Hemlibra) Clot-preserving medications Physical therapy First aid for minor cuts and bruises

46. Chronic lymphocytic leukaemia Chronic lymphoid leukemias include several disorders characterized by accumulation of mature lymphocytes, of either B cell or T cell type, in the blood. Of all the chronic lymphoid leukemias chronic lymphocytic leukemia is the most common with its peak incidence being between 60-80 years of age. It is a chronic lymphoproliferative disorder characterized by monoclonal B cell proliferation. Aetiology has been traced to genetic predisposition.

47. Pathophysiology The CLL tumor cell is a mature B cell with weak surface expression of immunoglobulin (IgM or IgD). CLL cells typically exhibit impaired apoptosis and a prolonged lifespan, and this is reflected in their accumulation in the blood, bone marrow, liver, spleen and lymph nodes.

48. Haematological findings Lymphocytosis Normochromic normocytic anaemia in later stages as a result of marrow infiltration or hypersplenism. Autoimmune haemolysis may occur. Thrombocytopenia Bone marrow aspiration shows up to 95% lymphocytic replacement of normal marrow elements. Trephine biopsy reveals nodular, diffuse or interstitial involvement by lymphocytes . Reduced serum immunoglobulin

49. Trephine biopsy showing nodular pattern of lymphocyte accumulation (left) Trephine biopsy showing diffuse increase in marrow lymphocytes- closely packed cells with small nuclei (right)

50. Management Investigations Complete blood count : to elicit lymphocytosis Bone marrow biopsy: to elicit malignancies Lymph node biopsy Genetic testing: to elicit abnormal genes Treatment Chemotherapy Targeted therapy: Radiotherapy Immunotherapy: immunomodulating agents, car-t cell therapy Stem cell transplantation

51. Chronic Myeloid Leukaemia This is a clonal disorder of a pluripotent stem cell known as the myeloid cells. The disease accounts for approximately 15% of leukaemia's and it occurs more in males than females (1.4:1) and frequently between the ages of 40-60 in either sex. However, it may occur in any age group.

52. Pathophysiology The condition results from the translocation between chromosomes 9 and 22, causing part of the oncogene ABL1 on chromosome 9 to move to the BCR (Breakpoint cluster region) gene on chromosome 22 and part of chromosome 22 moves to chromosome 9. The abnormal chromosome 22 is known as Philadelphia (Ph) chromosome. The resulting chimeric BCR-ABL1 gene codes for a fusion protein which has constitutively active tyrosine kinase activity in excess of the normal ABL1 product, resulting in uncontrolled proliferation.

53. Haematological findings Leucocytosis - The levels of neutrophils and myelocytes exceed those of blast cells and promyelocytes. Increased circulating basophils Normochromic normocytic Anaemia Platelet count may be increased (most frequently), normal or decreased Bone marrow is hypercellular with granulocytic predominance Elevated serum uric acid

54. Management Investigations Complete blood count Peripheral blood film BCR-ABL genetic test Cytogenic testing- for Ph chromosome Treatment Tyrosine kinase inhibitors Chemotherapy Stem cell transplant

55. INFECTION RELATED DISEASES

56. Human Immunodeficiency Virus (HIV) Human immunodeficiency Virus is an RNA and a r etrovirus. It attacks the body’s immune system. Globally, 38.4 million [33.9–43.8 million] people were living with HIV at the end of 2021. An estimated 0.7% of adults aged 15–49 years worldwide are living with HIV, although the burden of the epidemic continues to vary considerably between countries and regions. In 2021, 1.9 million people in Nigeria were living with HIV. Women were the most affected group, counting 1.1 million, while men counted 630,000. Also, children up to age 14 who were HIV positive equaled 170,000.

57. Haematological findings The haematological changes associated with HIV are wide ranged and tend to be worse in advanced forms of the disease- due to marrow defect and immune cytopenia, infection from an opportunistic infection, lymphoma and side effects of drug treatments. Anaemia Thrombocytopenia and neutropenia Increased plasma cells in the marrow and polyclonal increase in immunoglobulins Non-Hodgkin lymphoma

58. Management Investigations Complete blood count X-ray CT scan PET scan Lymph node biopsy Treatment Blood transfusions or recombinant erythropoietin injections Corticosteroids High-dose gamma globulin infusions Antiretroviral therapy Chemotherapy and immunotherapy

59. Malaria Malaria is an acute illness caused be infestation of the plasmodium parasite. It is a febrile illness that is spread through the bite of the female anopheles mosquito. There’s are five species of plasmodium that cause malaria in humans, P. vivax, falciparum, ovale, knowlesi, and malariae. P. Falciparum is the deadliest and the most prevalent in sub-Saharan Africa. Africa alone bears 95% of all malaria deaths worldwide, and 80% of all the deaths are of children under the age of 5. Of all the nations of the world, four of them bear the highest death rates, the nations being Nigeria, Democratic republic of Congo, Tanzania and Mozambique.

60. Pathophysiology The classical manifestations of malaria occur as a result of infection the red blood cells by asexual forms of the parasite. The parasite causes adherence of the red blood cells to the vascular endothelium. This causes sequestration of parasitized red blood cells in the capillaries and post capillary venues, causing micro-obstruction and tissue hypoxia. Due to the fact that the early developmental stages of the mosquito take place in stagnant water bodies, living near bodies of water such and lake and swamps predisposes an individual to a higher risk of malaria.

61. Haematological Findings Haematologically, the main manifestation of malaria is severe anaemia, which happens as a result of rupture of the red cells after multiplication of the parasite. This drops the haematocrit value and depending of the severity can go as low as 15%. The trophozoites can be seen arranged in a ring inside the infected red cells. They then rupture the cell and the daughter plasmodia infect ,ore cells. Oxidative stress also plays a roll in the death of red cells. Formation of haemoglobin metabolism derivatives which build up and can activate the coagulation pathway and trigger phagocytosis of infected red blood cells. In severe malaria, thrombocytopenia is usually in about 50-80% of cases. The presence of high molecular weight Von-Willebrand factor is a sign that there is associated vascular damage and platelet consumption. Leukopenia is a rather rare finding in blood films, only 8.8% of cases have such.

62. Microgram of the peripheral blood film of a malaria patient showing infected erythrocytes with the trophozoite stage of the Plasmodium falciparum parasite.

63. Management Investigations The important investigations in the diagnosis of malaria are a full blood count, with a microscopy test for the plasmodium that is suspected. FBC is usually low, with some form of leucocytosis occasionally. Microscopy will reveal trophozoites of P. falciparum present. Treatment Modern day management of malaria is via the use of ACT- Artemisinin combined therapy, using artemisinin analogues and other anti-microbial agents to clear the parasite and prevent resistance. Rehydration, rest and proper nutrition do go a long way in managing malaria. Blood transfusions can also be indicated in severe malaria where the PCV of the individual is dangerously low.