QUANTITATIVE AND QUALITATIVE ABNORMALITIES OF PLATELETS

Congenital abnormalities which includes:

1.               Fanconi’s   Anaemia: This is an autosomal recessive preleukaemic condition that often presents as thromobocytopenia with skeletal or genitourinary abnormalities.

2.               Giant granular platelets in peripheral blood film are seen in Bernard –soulier syndrome or may –Hegglin anomaly. Megakaryocytic thrombocytopenia presents with severe neonatal thrombocytopenia (platelet count < 2 x10⁹/L), though this often correct itself after the first year of

life.

3.               Wiskolt-aldrich syndrome: is an x-linked disorder with a triad of thrombocytopenia, eczema and immunodeficiency. The platelet count is usually 20-100×109/L and the platelets are functionally abnormal.

May Hegglin anomaly and variants of Alport’s syndrome are both characterized by giant platelets.

Diseases of the platelet storage pool are deficiencies in either in the α or dense granules causing poor secondary platelet aggregation.

Acquired Abnormalities

 Decrease production of platelets due to suppression of failure of the bone marrow is the commonest cause of the thrombocytopenia. In aplastic anaemia, leukaemia and marrow infiltration and after chemotherapy thrombocytopenia is usually associated with a failure of red and white cell production but may be an isolated finding secondary to drug toxicity (pencillamine,   costrimozazole, alcohol, malaria or viral infection (HIV, infectious mononucleosis).

Disorders with increased platelet consumption

i.        Disorders with immune mechanism;

a.           Autoimmune-idiopathic thrombocytopenia purpura

b.                     Alloimmune-post transfusion purpura

c.            Neonatal alloimmune-thrombocytopenia  

ii.     Infection –associated: infectious mononucleosis,  HIV,  malaria

iii.   Drug –induced, heparin, penicillin, quinine, sulphonamide  rifampicin

iv.   Thrombotic thrombocytopenic purpura/haemolytic   urmic  syndrome

v.      Hypersplensim and splenomegaly

vi.   Disseminated intravascular coagulation

vii. Massive transfusion  

Acquired disorders of reduced platelet production

a.         Drug induced  e.g  quinine, aspirin (Cheesbrough; 2006)

b.           Leukemia

c.           Metastatic tumor

d.          Aplastic anaemia

e.          Myelodysplasia

f.          Cytotoxic drugs

g.            Radiotherapy

h.            Infections  e.g  typhoid and other septicaemias (Cheesbrough; 2006) 

i.              Megalobalstic anaemia

j.              Due to bone marrow failure  or replacement 

Increased platelet consumption: May be due to immune or non immune mechanisms

a.        Idiopathic thrombocytopenic purpura is a relatively immune disorder and   the most frequent cause of isolated thrombocytopenia without anaemia or neutropenia. In this disorder autoantibody produced is usually LgG directed    against antigens on the platelet   membrane. The platelet lifespan is reduced to few hours. The  platelet count may vary from  < 5 x199/L  to near  normal,

b.         Spontaneous skin  purpura in  severe immune theombocytopenia  

c.        Bone marrow aspirate showing increased  magakaryocytes in  immune  thrombocytopenia

d.        Neonatal alloimmune thrombocytopenia is similar to haemolytic disease of the new born infants except   that the antigenic stimulus comes from platelet specific   antigens rather than red cell antigens.

Post –Transfusion Abnormality:

This is an acquired abnormality. It is a rare complication of blood transfusion presenting with severe thromobocytopenia 7-10 days after the transfusion. Patients are usually multiparous women who are negative for the human platelet antigen 1a. Antibodies to this antigen develop that are somehow responsible for   the immune destruction   of the patients own platelets.

Heparin induced thrombocytopenia occurs during heparin treatment in up to 5% patients. It may manifest when arterial or venous thrombosis occurs during a fall in the platelet and this is thought to be due the   formation of antibodies to heparin that are bound to platelet factor 4, a platelet granule protein. The immune complexes activate   platelets and endothelial cells, resulting in thrombocytopenia and thrombosis co-exiting.

Causes of Acquired Platelet Dysfunction;

1.              Aspirin and non-steroidal anti- inflammatory agents

2.              Penicillins and cephalosporins

3.              Uraemia

4.              Alcohol

5.              Liver disease

6.              Myeloprolifrative disorders

7.              Myeloma

8.              Cardiopulmonary bypass

9.              Fish oils

Thrombocytosis;

a.             Essential (primary) thrombocytosis

b.             Reactive (secondary) thrombocytosis

c.             Infection

d.             Malignant disease

e.             Acute and chronic inflammatory diseases

f.              Pregnancy

g.             After splenectomy

h.             Iron deficiency

i.               Hemorrhage

In essential (primary) thrombocytosis and reactive (2^o) thrombocytosis, the platelet count is raised above the upper limit of normal.

Abnormalities of blood stored in anticoagulants include tetany of muscles, decreased packed cell volume (PCV), increased mean cell volume (MCV), artificial increase in Platelet count (PC) and decrease white blood cell (WBC) count (Gossens et al; 1991),(Dacie and Lewis; 1994).