Thrombopoiesis and thrombogram Flashcards
(13 cards)
Thrombopopiesis
Platelets derived from megakaryocytes in the bone marrow (and spleen)
Production regulated by thrombopoietin (TPO)
TPO secreted by hepatocytes and renal tubular cells at a constant rate, and cleared by platelets and megakaryocytes (less platelets -> more TPO -> more platelets)
TPO production also increased in inflammation
Circulation time of platelets
Circulate for around 6 days - cleared by liver and spleen
Up to 20-30% can be sequestered by spleen
Production takes around 3 days
Interpretation of the thrombogram
Requires evaluation of blood smear as plaelet clumps not counted (occur commonly, esp in cats) - pseudothrombocytopaenia
Some animals also have large platelets which leads to pseudothrombocytopaenia e.g. CKCS
Sighthounds normally have low platelet counts
Thrombocytopaenia causes
Pseudothrombocytopaenia (platelet clumping, macroplatelets, breed - sighthound)
Blood loss
Increased consumption
Increased destruction
Decreased production
Sequestration
Consumptive thrombocytopaenia
Seen in DIC - in severe inflammatory disorders
Inflammation activates coagulation cascade - platelets incorporated into clots all over the body
Often marked thrombocytopaenia
Other haematological features of DIC - inflammatory leukogram, prolonged coagulation times (OSPT APTT)
Accelerated destruction/loss of platelets
Immune mediated attack of the platelets by the body, immune mediated thrombocytopenia (IMTP).
Antibodies directed against cell surface antigens on platelets will cause premature destruction of platelets by macrophages (phagocytosis).
IMTP can be primary (idiopathic) or secondary to drugs (such as trimethoprim sulphonamides), neoplasia, or infectious agents (such as A. phagocytophilum, Babesia spp., Ehrlichia spp., Leishmania spp.).
Immune mediated thrombocytopaenia (IMTP)
Primary IMTP is common in dogs, but uncommon in cats.
Some breeds are predisposed including Cocker spaniels, miniature poodles and Old English Sheepdogs.
Young to middle aged female dogs are also more commonly affected.
Clinical signs of IMTP
Relate to those expected in disorders of primary haemostasis (e.g. petechiation, melaena, epistaxis).
If bleeding occurs in the ocular or CNS tissues then neurological signs (e.g. seizures, ataxia) or blindness may occur.
These dogs can also be lethargic, pyrexic, and uncommonly have hepatosplenomegaly and/or lymphadenopathy.
Diagnosis of IMTP
· Severe thrombocytopenia (<30 x10^9/L)
· Neutrophilia (+/- left shift) and anaemia (which may reflect IMHA or haemorrhage secondary to bleeding associated with thrombocytopenia)
Definitive diagnosis is only possible if anti-platelet antibodies can be demonstrated, however this test is not widely available and is subject to false positive and false negative diagnoses and so is not recommended for diagnosis of IMTP.
Diagnosis is therefore often made on the basis of exclusion of other possible causes of thrombocytopenia (bone marrow disease, consumption), and other causes of secondary IMTP (e.g. drugs exposure, infections, neoplasms), from history, clinical examination, other blood results and imaging.
Reduced platelet production (bone marrow disease)
Usually associated with other cytopenias (anaemia, neutropenia).
Causes:
· Drugs – chemotherapy, oestrogens, phenylbutazone, trimethroprim sulphonamides, chloramphenicol
· Myelophthesis – lymphoproliferative disease (lymphoma, leukaemia, multiple myeloma), metastatic neoplasia, myelofibrosis
· Infections – FeLV, FIV, feline panleukopaenia virus, FIP in cats, Distemper, parvovirus, Anaplasma phagocytophilum, Ehrlichia, Babesia, Leishmania
· Other - immune mediated destruction of platelet precursors is very rare
Sequestration of platelets
Around a third of platelets are sequestered in the spleen at any one time, therefore any condition which causes splenomegaly can result in decreased platelet counts but the reduction is usually mild (not <100x10^9/L) and not clinically important.
Splenomegaly may be caused by congestion (portal hypertension, splenic torsion), chronic infectious or inflammatory disorders, and neoplasia.
Hypothermia and sepsis can also cause platelet sequestration.
Platelet losses
Blood loss tends to not influence platelet count unless the bleeding is severe (e.g. with rodenticide toxicity), and even in these situations, the thrombocytopenia is usually only mild (not <100x10^9/L) and transient.
Thrombocytosis
Release of platelets from spleen (sequestered stores) in response to excitement/catecholamines
Increased production in bone marrow secondary to:
○ Inflammation (chronic) due to increased TPO
○ Iron deficiency (pathogenesis uncertain)
○ Vincristine (increase platelet production from megakaryocytes)
○ Rebound thrombocytosis following previous thrombocytopenia
Splenectomy (less phagocytosis of old platelets)
Megakaryocyte neoplasia
Thrombosis can cause artefactual hyperkalaemia check using lith hep sample (prevents clotting)
