Platelet Disorders
in Companion Animals
Julien Dandrieux Internal Medicine Resident Louisiana State University jdandrieux@mail.vetmed.lsu.edu
Objectives
Become familiar with
clinical presentations of platelet disorders tests for evaluation of platelet disorders
Identify diseases causing primary hemostasis defect
thrombocytopenia thrombocytopathy Von Willebrand’s disease (vWD)
Definitions
Hemostasis: arrest of the escape of blood (primary and secondary hemostasis) Thrombocytopenia: decrease in number of platelets in circulating blood Thrombocytopathy: any qualitative disorder of blood platelets
H E M O S T A S I S
Primary
Platelets Tissue factors
Secondary
Coagulation factors
Clinical Presentation
Clinical Presentation
Most common clinical sign is bleeding of some sort
External loss
Epistaxis, hematuria, GI bleeding
Internal loss — skin, mucous membranes, retina
Petechiae, ecchymosis, hematoma
Manifestations of platelet disorders
Clinical Presentation
Most common clinical sign is bleeding in some form
External loss
Epistaxis, hematuria, GI bleeding
Internal loss — skin, mucous membranes, retina
Petechiae, ecchymosis, hematoma
Manifestations of platelet disorders
Manifestations of platelet disorders
Evaluation of bleeding disorders
Evaluation of bleeding disorders
History
Vaccination, drug, infection
CBC with differential and platelet count
Manual count important if clumping, large platelets Coagulation panel (PT, PTT), BMBT, vWF concurrent disease, hematuria Platelet production, concurrent disease
Hemostasis
Chemistry panel, Urinalysis
[Bone marrow]
Evaluation of Bleeding Disorders
Test
Platelet count
Parameter
Platelet quantity
Normal Function
1ary hemostasis
BMBT
vWF assay
Platelet function
vWF
1ary hemostasis
1ary hemostasis
PTT PT
Coagulation (in.) Coagulation (ex.)
2ary hemostasis 2ary hemostasis
Evaluation of Bleeding Disorders
Test
Platelet count
Parameter
Platelet quantity
Normal Function
1ary hemostasis
BMBT
vWF assay
Platelet function
vWF
1ary hemostasis
1ary hemostasis
PTT PT
Coagulation (in.) Coagulation (ex.)
2ary hemostasis 2ary hemostasis
Platelet count (CBC)
Platelet count
Falsely decreased: clumping (C), large platelets (C)
Platelet morphology
Mean platelet volume (MPV) Platelet distribution width (PDW)
Platelet estimate
10-30 platelets per 100x fields Severe bleeding with 0-3 platelets per 100x fields
Platelet morphology
CLUMPING ITP, IMHA
Buccal mucosal bleeding time (BMBT)
Information about platelet function! Normal: 1.8 to 4.2 minutes
Platelets and bleeding
Low platelet number = Thrombocytopenia < 50,000/ml Below 25,000-30,000/ml is critical point
VS
Platelet dysfunction = Thrombocytopathy
Thrombocytopenia
Most commonly recognized hematological disorders in veterinary medicine
Thrombocytopenia
Decrease production
Sequestration
Increased utilization
Destruction
Decreased production
Various causes Marrow aplasia /myelofibrosis Marrow infiltrate—neoplasia Marrow suppression—drug, infection, toxin
Bone marrow aspiration Decreased megakaryocytes (MK) (aspiration/core) Usually other cell lines are also affected
Decreased production
Treat the underlying disease if possible Remove drug source Treat infection Treat neoplasia Supportive care (no injuries!!)
Thrombocytopenia
Decrease production Increased utilization
Sequestration
Destruction
Bone marrow disease - Infection - Toxin - Drug - Neoplasia
Sequestration
Hypersplenism Platelet mass is normal, but platelets are sequestered in the spleen Occurs secondary to splenomegaly due to immune-mediated disease, neoplasia, infectious disease Clinical significance? No MK increase because no decrease in platelet mass
Thrombocytopenia
Decrease production Increased utilization
Sequestration
Destruction
MK diminished - Infection - Toxin - Drug - Neoplasia
MK normal - Possible endotoxemia - Drug? - Clinical relevance?
Increased Utilization
Severe blood loss Trauma Mild thrombocytopenia (up to 120,000/ml) Anemia, hypoalbuminemia, hypovolemic choc Disseminated intravascular coagulopathy (DIC) Secondary (neoplasia, liver disease, pancreatitis) Chemistry, PT, PTT, D-dimers, ATIII
Increased Utilization
MK: adequate or hyperplasia in most cases Treatment Severe blood loss Fluids, blood products + surgery DIC Treating underlying disease Plasma
Thrombocytopenia
Decrease production Increased utilization
Sequestration
Destruction
MK diminished - Infection - Toxin - Drug - Neoplasia
MK normal - Possible endotoxemia - Drug? - Clinical relevance?
MK normal/increased - Blood loss - DIC
Destruction
Immune mediated thrombocytopenia (ITP) Primary
autoantibody directed against antigen on the platelet membrane
Secondary
Most common cause of thrombocytopenia Associated with underlying condition: Systemic autoimmune disease, neoplasia, infection, vaccination
Primary ITP—Clinic
Breed Cocker spaniel GSD Poodles
Usually young to middle-aged dogs F >> M
Can remain asymptomatic!!
Primary ITP—Laboratory
Severe Thrombocytopenia (<30,000/ml) Increase proportion of small or large platelets Anti-platelet antibody MK Usually hyperplasia Decreased if also antibodies against MK
Antimegakaryocyte antibody test
Primary ITP—Treatment
Exclusion of secondary causes
Immunosuppression Corticosteroids, azathioprine, cyclosporine (Cyclophosphamide, vincristine??)
Platelet rich plasma
Splenectomy Spleen is primary site of platelet removal Does not correct underlying cause
Secondary ITP—Causes
Drug induced Sulfa antibiotics, estrogen, acetaminophen, phenylbutazone
Infectious agents Viral (FeLV, parvovirus), Rickettsial (Ehrlichia spp., RMSF, Mycoplasma) Bacterial (Leptospira, Salmonella) Protozoal (Babesia, Leishmania, Toxoplasma, Cytauxzoon spp.) Fungal (Histoplasma capsulatum, Candida albicans)
Secondary ITP—Causes
Other immune-mediated diseases Systemic lupus erythematosus
Vaccinations (modified live vaccines, transient) Neoplasia (Rule out DIC, bone marrow involvement!) Lymphoma Multiple myeloma
Secondary ITP—Treatment
Remove inciting cause Discontinue drug therapy Treat the underlying disease Antibiotics, antifungals Chemotherapy, surgery, RT Immunosuppression
Thrombocytopenia
Decrease production Increased utilization
Sequestration
Destruction
MK diminished - Infection - Toxin - Drug - Neoplasia
MK normal - Possible endotoxemia - Drug? - Clinical relevance?
MK normal/increased - Blood loss - DIC
MK normal/decreased - Primary - Secondary
Thrombocytopathy
Thrombocytopathy
Decreased function of platelets despite adequate platelet number Platelet count often normal, may even be increased Clinically detectable bleeding may occur at any platelet count Megakaryocytes usually normal to increased
Clinical Evaluation
Buccal mucosal bleeding time Perform in cases with normal coagulation times, normal platelet count, but clinical evidence of bleeding or past coagulation issues Prolonged in cases of platelet dysfunction
Classification
Congenital Von Willebrand factor (vWF) Platelet membrane/granule abnormality Acquired Drugs Systemic disease
Congenital disorders
von Willebrand’s disease (vWD)
Most common inherited disorder of hemostasis
Glanzman’s thrombopathia
Otterhounds Great Pyrenees
Basset Hound thrombopathia Scott syndrome
von Willebrand’s disease
vWf function
Platelet aggregation Decrease number and normal structure
Cause
Type I
Type II Type III
Dobermann, Airedale Terrier, Rottweiller
German Wirehair, Shorthair Pointers Shetland Sheepdog, Chesapeake Bay Ret.
Decrease number and abnormal structure
Absolute vWf deficiency
von Willebrand’s disease
Laboratory findings
Platelet number: PT, PTT: BMBT: vWf concentration:
NORMAL NORMAL PROLONGED DECREASED
von Willebrand’s disease
Treatment Screen predisposed breeds prior to surgical procedures
BMBT vWf immunoassay
Fresh frozen plasma prior surgery Desmopressin-administered SQ prior to surgery
Acquired : Drug induced
NSAIDs Anesthetics (halothane) Antibiotics (penicillin, cephalothin) Calcium channel blockers (diltiazem) Anticoagulants (heparin) Many others…
Acquired : systemic disease
Uremia Monoclonal gammopathy DIC Hepatic disease Neoplasia
Conclusions
Primary hemostasis testing
Platelet count (-penia) BMBT (-pathy)
Thrombocytopenia
Most common acquired haemostatic disorder Decrease production/sequestration/utilization/destruction Bleeding, petechiae and ecchymoses
Von Willebrand’s disease
Example of thrombocytopathy (BMBT) Most common inherited disorder of hemostasis Common in Doberman
Questions?