Blood system

• peripheral blood• organs of blood formation and destruction• neurohumoral mechanisms of regulation of these

processes

Scheme of hemopoiesisS – pluripotent stem cell (original cell giving rise to other specific cell)

HS – hemopoietic cell

LS – lymphoid stem cell

T – thymus gland cell

B – bone-marrow derived cell

MK – megacaryocyte

ES – erythroid stem cell (source of red blood cells)

MS – myeloid stem cell (source of various white cells)

GS – granulocyte stem cell (source of specific white blood-cell types)

Parameters on peripheral full blood count in health (1)

• ESR m 1-10 mm/hf 2-15 mm/h

• Haemoglobin (Hb) m 130-169 g/Lf 120-155 g/L

• Colour index 0.85-1.05• Red blood cells (RBC) m 4.0-5.8×1012/L

f 3.7-5.2×1012/L• Packed cell volume m 40-50 %

(haematocrit, Hct) f 36-47 %• Platelets 150-450 ×109/L• Reticulocytes (Rt) 2-12 ‰• White blood cells (WBC) 4.0-9.0×109/L

Parameters on peripheral full blood count in health (2)

•blasts absent•myelocytes absent•metamyelocytes absent•stab (band) neutrophils 1-5 %•segmented neutrophils 45-72 %•eosinophils 0-5%•basophils 0-1 %•lymphocytes 18-40 %•monocytes 2-10 %•plasma cells absent

The differential white count

•anaemic syndrome•haemorrhagic syndrome•hepatolienal syndrome•lymphadenopathic syndrome•febrile syndrome•arthralgic (arthrodynic) syndrome•necrotic (sphacelous) syndrome•septic syndrome

Clinical features of blood system diseases

• acute posthemorrhagic anaemia

• chronic posthemorrhagic anaemia

I. Anaemias due to blood loss

Main pathogenic mechanism of posthemorrhagic anaemia is decrease of red cell mass.

• iron deficiency anaemia

• vitamin B12 (folate)- deficiency anaemia

• hypo- and aplastic anaemia• metaplastic anaemia (due to replacement of bone

marrow by leukaemia, tumour metastasis)

II. Anaemias due to decreased red cell production

• congenital haemolytic anaemia

• acquired haemolytic anaemia

III. Anaemia due to increased red cell destruction

Main pathogenic mechanism of haemolytic anaemias is shortened red cell survival (in norm erythrocyte’s life span ranges from 100 to 120 days).

Causes of iron-deficiency anaemias (1)

• chronic blood loss • achlorhydria, achylia, gastric cancer, gastrectomy leading to

disturbance of iron ionization in stomach and, correspondingly,

iron absorption • malabsorbtion due to duodenitis and enteritis • pregnancy and lactation leading to increased requirement for

iron and exhaustion of its supply in tissues• nutritional deficiency (e.g., strict vegetarians)

All causes lead to negative iron balance, decreased transferrin saturation and disturbance of normal erythropoesis

Causes of iron-deficiency anaemias (2)

• menstruation• GI tract• urinary tract

Chronic blood loss

• permanent• long-term• small volume• unnoticed

Causes of vitamin B12-(folate)- deficiency anaemias

• nutritional deficiency of vitamin B12

• intrinsic factor deficiency due to achlorhydria, achylia in

autoimmune damage of parietal cells (Addisonian

pernicious anaemia), gastric cancer, gastrectomy

• disturbance of vitamin B12 absorption in the terminal ileum

in the presence of enteritis, worm invasion, terminal ileum

removal

• increased requirement for vitamin B12 in pregnancy

• liver diseases (cirrhosis, hepatitis, carcinoma) leading to

disturbance of folic acid activation in liver

• congenital abnormalities of red cells• exogenous impacts on erythrocytes

• hemolytic disease of newborn (Rh-baby)• toxic causes (severe burns, hemolytic poisons, etc.)• infections • transfusion-related damage of red cells (incompatible

blood transfusion)• autoimmune damage of red cells• any splenomegaly

Causes of haemolytic anaemias

• dizziness• tinnitus• tendency to faints• fatigue• reduced exercise capability

Symptoms due to brain dysfunction

Anaemic syndrome (1)

•shortness of breath•palpitation•tachycardia

Manifestation of compensatory intensification of respiration and circulation

Anaemic syndrome (2)

Pallor of the skin and mucous membranes

Anaemic syndrome (3)

• body temperature• blood pressure level• volume and tension of pulse

Tendency to decrease of

Anaemic syndrome (4)

• innocent soft systolic murmurs over heart• permanent Nun’s murmur over jugular veins in

profound anaemia

Anaemic syndrome (5)

• decrease of haemoglobin level lower than 120-130 g/l or/and

• decrease of red cell-count lower than

3.7-4.0×1012 in 1 litre of blood

Anaemic syndrome (6)

• normocytosis – red cells of normal size (7.2-8.0 µm)

• microcytosis – red cells of smaller size (≤7.0 µm)

• macrocytosis – red cells of larger size (>8.0 µm)

• megalocytosis – red cells of very large size (11.1-15.0 µm)

• anisocytosis – increased variations in red cell size (feature of any anaemia)

Red cell size

• poikilocytosis – increased variation in red cell shape (feature of profound anaemia)

•echinocyte•sickle cell•acanthocyte•target cell•teardrop cell•spherocyte and etc.

Red cell shape

Certain shapes are diagnostic for certain conditions:

• normochromia – normal colouration and normal haemoglobin content in RBC

• hypochromia – large area of central pallor and low haemoglobin content in RBC (frequent combination with microcytosis)

• hyperchromia – small area of central pallor and high haemoglobin content in RBC (frequent combination with macrocytosis)

Red cell coloration and colour index

Reflect haemoglobin content in red cells

• microcytosis• hypochromia of RBC• low colour index (<0.8)• anisocytosis and

poikilocytosis of RBC• normal white-cell count• normal platelet count

Iron-deficiency anaemia

Full blood count

Blood serum• low content of iron• high total iron-binding capacity• low ferritin level

• macrocytosis, megalocytosis• hyperchromia of RBC• high colour index• anisocytosis and poikilocytosis• red cells with nuclear remnants (Howell-Jolly bodies,

Cabot’s ring bodies)• reticulocytopenia• hypersegmentation of neutrophil nuclei (“right shift”)• leucopenia (neutropenia)• thrombocytopenia• megaloblastic hemopoiesis• neurological lesions in posterior and lateral columns of the

spinal cord (due to disturbance of fatty acid metabolism in vitamin B12 deficiency)

Vitamin B12-(folate)-deficiency anaemia

Haemolytic anaemia• reticulocytosis• normal colour index

(except for thalassaemia)• presence of nucleated red

cells in peripheral blood • normal white-cell count

(neutrophilic leucocytosis in hemolytic crises)

• normal platelet count

Full blood count

Other

• unconjugated hyperbilirubinemia• splenomegaly

Aplastic anaemia• normochromic normocytic (rarely

hyperchromic macrocytic) anaemia• reticulocytopenia (up to complete

absence of reticulocytes)• neutropenia and leucopenia• thrombocytopenia of various degree• aplastic bone marrow (replacement of

normal haemopoietic cells by fat)• fever, infectious complications, ulcero-

necrotic lesions of mucous membranes• hemorrhagic syndrome

Hemorrhagic syndrome (1)

• presence of various hemorrhages on skin and mucosal surfaces

• various bleeding (epistaxis, menorrhagia, bleeding gums, GI, etc.) and haemorrhages into internal organs (brain, retina, joints)

Clinical manifestation

Pathological condition that is characterized increased bleeding tendency.

Hemorrhagic syndrome (2)

• thrombocytopenia• coagulation defects• increased vascular

permeability (capillary fragility)

Main causes

Hemorrhagic syndrome (3)

• character and type of hemorrhages• Rumpel-Leede test • tests of coagulation• features of platelet-vascular hemostasis

Diagnostics

Rumpel-Leede test: a circle 2.5 cm in diameter, the upper edge of which is 4 cm below the crease of the elbow, is drawn on the inner aspect of the forearm, pressure midway between the systolic and diastolic blood pressure is applied above the elbow for 15 minutes, and a count of petechiae within the circle is made: 10, normal; 10 to 20, marginal zone; over 20, abnormal.

Hemorrhagic syndrome (4)

• hemorrhages as petechiae or ecchymosis

• frequent bleeding or hemorrhages into internal organs

• positive Rumpel-Leede test• thrombocytopenia

(count < 50-100.0×109/l)• absence of coagulation test

abnormalities

Thrombocytopenic purpura

Haemoblastosis

• leucaemic (leucaemias)

• haematosarcomas• lymphosarcomas• lymphomas

• non-leucaemic

• acute• chronic

Classification

Leukaemias (1)

• neoplastic clonal proliferation of one cell line (myeloid, lymphoid, etc.)

• decrease (in chronic leukaemias) or almost complete absence (in acute leukaemias) of cytodifferentiation leading to appearance of the immature and abnormal leukaemic cells in bloodstream circulation

• bone marrow metaplasia associated with removal of other cell lines (mostly erythroid or thrombocytic lines)

• development of leukaemic infiltrations in various organs – pathological accumulation of neoplastic blood cell of proliferating cell line due to their metastases in these organs

Haematological manifestation

Leukaemias (2)Clinical manifestation

• Proliferative syndromes

• haemopoietic tissue hyperplasia (enlarged lymph nodes, splenomegaly, hepatomegaly)

• arising of foci of extramedullary haemopoisis (skin rashes, bone and joint pain, tenderness during bone percussion, etc.)

Leukaemias (3)

• anaemic syndrome• haemorrhagic syndrome• increased susceptibility to infections due

to lowered immunologic tolerance

Clinical manifestation

• typical changes in full blood count

infectious-septic and ulcero-necrotic lesions in lungs, kidneys, tonsils and other organs

Leukaemias (4)

• full blood count including blood film, differential white cell count, platelet and reticulocyte count in 1 μl of blood, erythrocyte sedimentation rate (ESR)

• bone marrow examination (aspirate from the sternum or iliac crest and trephine biopsy from the iliac crest)

• cytochemical examination of blasts• lymph node biopsy with cytologic and histologic study• immune-enzyme analysis of haemopoietic cells by

monoclonal antibodies• immunoelectrophoresis of blood and/or urine• radiological methods• clotting tests (prothrombin time, activated partial

thromboplastin time, thrombin time)

Haematological methods of examination

Acute leukaemias (1)

• lymphoblastic • myeloid• promyelocytic• monocytic• myelomonocytic• erythroblastic (erythromyelosis)• megakaryoblastic• plasmacytoblastic• non-differentiable

Classification

It is characterised by excessive proliferation of one dominant cell line and almost complete absence of cytodifferentiation or this cell line

Acute leukaemias (2)Peripheral blood

• elevated white-cell count up to 100.0×109/l (leukopenic forms are possible)

• presence of blasts (primitive cells) in peripheral blood in large numbers

• leucemic gap or hiatus (maturation arrest)

• normochromic normocytic anaemia

• thrombocytopenia

Chronic leukaemias

• chronic granulocytic leukaemia

• polycythaemia vera (erythraemia)

• Myeloproliferative diseases

Classification

• chronic lymphocytic leukaemia

• paraproteinemic haemoblastosis• multiple myeloma

• Lymphoproliferative diseases

Main substratum of these tumors are formed by morphologically mature cells of corresponding cell line.

Chronic granulocytic leukaemia

Full blood count

• elevated white-cell count (up to 200.0-300.0×109/l)

• circulation of all transitional forms (midstage progenitor cells) of myeloid cells from occasional myeloblasts and promyelocytes to mature neutrophils in peripheral blood (whole spectrum of myeloid precursors)

• associated increase in eosinophils and basophils

• mild-to-moderate normochromic anaemia• elevated platelet count (thrombocytosis)

in early stages of disease, in end-stage - thrombocytopenia

Polycythaemia vera

Full blood count

• increased haemoglobin concentration up to 180-200 g/l and more

• increased number of red cells (up to 7.0-8.0×1012/l)

• raised haematocrit in the range 50-70%

• moderate neutrophilic leukocytosis • thrombocytosis• slowed down ESR

Chronic lymphocytic leukaemiaFull blood count

• elevated white-cell count (up to 30.0-200.0×109/l and more)

• increased number of lymphoid line cells (up to 60-90% from total white-cell number), mainly due to mature lymphocytes and only partially due to lymphoblasts and prolymphocytes

• presence of smudge (shadow) cells• normochromic anaemia• thrombocytopenia

Multiple myeloma

Criteria

• normochromic anaemia• high ESR up to 70-80 mm/h• plasma cell infiltration of bone

marrow • presence of paraprotein in blood

serum and/or urine • bone destruction

Leukemoid reaction

Inflammation

• elevated white-cell count up to 15.0-50.0×109/l

• neutrophilic leucocytosis with “left shift”• raised ESR • heavy granulation of neutrophils• signs of infection, usually bacterial

A moderate, advanced, or sometimes extreme degree of leukocytosis in the circulating blood, similar to that occurring in various forms of leukaemia, but not the result of leukaemic disease.

Agranulocytosis

• decrease of total white-cell count below 1.5-3.0×109 cells/L• decrease of absolute neutrophil-count below 0.75 ×109

cells/L• normal red-cell count• normal platelet count• fever, infectious complications, ulcero-necrotic lesions of

mucous membranes• absence of cells of granulocytic line in bone marrow

An acute condition characterized by pronounced leukopenia with great reduction in the number of polymorphonuclear leukocytes

Erythrocytosis

• increased haemoglobin concentration up to 160 g/L and more

• increased number of red cells (up to 6.0-6.5×1012/L)• normal white-cell count and platelet count

Increased number of red blood cells, especially that which occurs in response to some known stimulus (e.g. hypoxia)