Transcript Haematological aspects of systemic disease

Haematological aspects of
systemic disease
Overview
Inflammation – malignancy
Renal, liver, endocrine,pregnancy
Infection, amyloid
Inflammation - Malignancy
Anaemia of chronic disease
(ACD)
Normochromic or mildly hypochromic
anaemia
Moderate anaemia (hb>9.0g/dl)
Reduced serum iron and tibc
Normal or raised serum ferritin with
adequate bm iron stores and reduced
sideroblasts
Conditions associated with anaemia of chronic
disorders
Chronic infections
Especially osteomyelitis, bacterial endocarditis, tuberculosis, chronic
abscesses, bromchiectasis, chronic urinary tract infections, HIV, AIDS,
malaria.
Other chronic inflammatory disorders
Rheumatoid arthritis, polymyalgia rheumatica, systemic lupus erythmatosus,
schleroderma, inflammatory bowel disease, thrombophlebitis.
Malignant diseases
Carcinoma, especially metastatic or associated with infection, lymphoma
Others
Congestive heart failure, ischaemic heart disease
Pathogenesis of ACD
Pathogenesis of ACD
Hepcidin
Increased levels of cytokines
Treatment
Therapy of chronic disease
Recombinant EPO
Malignancy - anaemia
ACD affects almost all patients
AIHA esp. in lymphoma
MHA with disseminated
Blood loss in GI and gynaecological malignanciesmucin secreting
adenocarcinoma
Leucoerythroblastic anaemia indicates marrow infiltration
Red cell aplasia is associated with thymoma, lymphoma and CLL
Other causes
Chemotherapy or radiotherapy
Folate deficiency
Malignancy
Polycythaemia
Tumour cells may produce EPO or EPO-like polypeptides
White cell changes
Neutrophilia (infection or bleeding)
Neutropaenia (chemotherapy)
Platelets
Thrombocytopaenia
Thrombocytosis
Coagulation changes
Haemorrhage or thrombosis (activation of both coagulation
and fibrinolysis)
Chronic DIC - thrombosis and migratory thrombophlebitis
Circulating anticoagulants and specific coagulation factor
inhibitors
Connective tissue disorders
Anaemia
ACD common. Fe def. may coexist
AIHA occurs in SLE, R.A, and mixed CTD
Red cell aplasia occurs in SLE
White cells
Inflammation – neutrophilia
Felty’s sx. (neutropaenia with splenomegaly in R.A
Antibody and immune mediated neutrophil destruction and
decreased neutrophil production
Eosinophilia – SLE, R.A, polyarteritis nodosa
Platelets
Thrombocytopaenia
Thrombocytosis in CTD
CTD – cont.
Coagulation changes
Associated with renal disease, drug therapy, DIC and specific
coagulation factor inhibitors
The Lupus anticoagulant occurs in approximately 10% of patients
with SLE.
Renal, Liver, Endocrine Pregnancy
Renal disease
Anaemia
Acute or chronic renal failure – normochromic normocytic anaemia
Reduce EPO levels
Echinocytes
Iron deficiency and haemolysis (HUS & TTP)
EPO corrects anaemia to 12g/dL
Poor response to EPO –
fe or folate def. , haemolysis, infection, occult malignancy,
aluminium toxicity, hyperparathyroidism and inadequate dialysis
Hypertension and thrombosis of an AV fistula may occur
Polycythaemia
May occur with renal tumours or cysts
Renal disease
Haemostatic abnormalities
Coagulation factors II, XI or XIII may be reduced
Platelet function is impaired (predisposed to bleeding)
Low levels of Protein C, AT or plasminogen may lead to
thrombosis
Endocrine disease
Anaemia
Hyper and hypothyroidism cause a mild anaemia (MCV raised in
hypothyroidism and lowered in thyrotoxicosis)
Deficiencies of iron, as a result of menorrhagia or achlorhydria
B12 deficiency (increased incidence of pernicious anaemia in
hypothyroidism, hypoadrenalism and hypoparathyroidism) kay
complicate the anaemia
Anti-thyroid drugs (carbimazole and propylthiouracil) can cause
aplastic anaemia and agranulocytosis
Liver disease
Anaemia
Caused by anaemia of chronic disease, haemodilution (increased
plasma volume), pooling of red cells (splenomegaly) and
haemorrhage (e.g. oesophageal varices)
MCV raised especially in alcoholics
Target cells, echinocytes and acanthocytes occur
Haemolysis and hypertriglyceridaemia with alcoholic liver disease is
rare
Direct toxicity of copper for red cells causes haemolysis in Wilson’s
disease
Viral hepatitis may lead to aplastic anaemia
Platelets may be low (hypersplenism or DIC)
Liver disease cont.
Platelets and haemostasis
Defects of platelets, coagulation and fibrinolysis
Reduced synthesis of Vit. K. dependent factors (II,VII,IX,X,pC,pS)
Impaired synthesis of other coagulation proteins (I,V)
Thrombocytopaenia (hypersplenism) and abnormal platelet
function (cirrhosis)
Fibrinolysis impaired
Reduced levels of proteins C,S,AT, antiplasmin – DIC
Dysfibrinoginaemia may lead to haemorrhage, or thrombosis
Coagulation changes
Increased PT,APTT, N or increased TT, decreased platelets and
dysfibrinogenaemia
Pregnancy
Anaemia
Plasma volume increases up to 50%, RCM increases 20-30% haemodilution, MCV rises
Fe. def. frequent (RCM, fe. to foetus, blood loss)
Increased folate requirements (catabolism) ,B12 falls below normal
AIHA, HELLP syndrome, DIC
White cells
Mild neutrophil leucocytosis with left shift
Platelets
Gestational Thrombocytopenia
Maternal ITP
Pre-eclampsia
Coagulation changes
Increased risk of thrombosis and DIC
Infection, Amyloid
Infection - viruses
Anaemia
AIHA
Erythema variegata (fifth disease) - B19 Parvovirus
Virus associated bone marrow aplasia (Hep, HIV, CMV)
MAHA with TTP
White cells
Neutropaenia with lymphopaenia or lymphocytosis
Platelets
Thrombocytopenia – either immune (infectious mononucleosis,
HIV) , caused by bone marrow aplasia, or increased consumption
(e.g. DIC, TTP,HUS, Haemophagocytosis)
Reactive thrombocytosis
Infection – bacterial, fungal and
protozoal
Anaemia
ACD is frequent.
Haemolytic anaemia may be immune or non-immune.
DIC and MAHA may occur. HUS may follow infection by E.coli,
Shigella and Campylobacter.
Blood loss can occur with H.pylori and ankylostoma infections.
White cells
Neutrophilia is most common.
Platelets
Thrombocytosis is frequently reactive. Thrombocytopenia may also
occur, caused by immune destruction, circulating immune
complexes, decreased platelet production and DIC
Haemostasis
DIC
Infection – bacterial, fungal and
protozoal cont.
Malaria
Anaemia is caused by haemolysis, splenic sequestration,
haemodilution and ineffective erythropoeisis.
Malaria antigens attached to red cells may cause immune
haemolysis. Acute intravascular haemolysis with haemoglobinuria
and renal failure (blackwater fever) occurs rarely in Plasmodium
falciparum. ACD may also occur.
Eosinophilia is variable.
Thrombocytopenia may be caused by immune destruction, splenic
sequestration and DIC.
Leishmaniasis
Protozoal infection
Hepatosplenomegaly, hypergammaglobulinaemia, normochromic
anaemia and a raised ESR occur.
Amyloid
Tissue deposition of a homogenous eosinophilic protein material
which is birefringent and stains with Congo red.
2 types
Amyloid derived from clonal lymphocyte or plasma cell proliferation
(AL) (e.g. myeloma, primary amyloidosis)
Reactive amyloidosis (AA) which occurs when serum amyloid A
protein is deposited in chronic inflammatory disease (e.g.
rheumatoid arthritis, inflammatory bowel disease) or chronic
infection (e.g. tb, leprosy, osteomyelitis and bronchiectasis)
Localized amyloid may occur
Amyloid P protein is deposited in both AL and AA types
Amyloid deposition leads organ enlargement and dysfunction.
Tissues involved include: kidneys, heart, skin, tongue, endocrine
organs, liver, spleen, GI tract, respiratory tract and the autonomic
nervous system.