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Practical Hematology Diagnosing Coagulopathy

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Title: Practical Hematology Diagnosing Coagulopathy


1
Practical HematologyDiagnosing Coagulopathy
  • Wendy Blount, DVM

2
Practical Hematology
  • Determining the cause of anemia
  • Treating regenerative anemias
  • Blood loss
  • Hemolysis
  • Treating non-regenerative anemias
  • Blood plasma transfusions in general practice
  • Determining the causing of coagulopathies
  • Treating coagulopathies in general practice
  • Finding the source of leukocytosis
  • Bone marrow sampling

3
Hemostasis
  • Primary hemostasis
  • Platelets plug up damaged blood vessels
  • Von Willebrand Factor (vWF)
  • Vasoconstriction
  • Secondary hemostasis
  • Platelet plug organized by fibrin
  • Fibrin generated by coagulation cascade (factors)
  • Fibrinolysis

4
Coagulopathies
  • Poor Clotting
  • Not enough hemostasis
  • Problem with primary and/or secondary hemostasis
    so that clots do not form and stabilize normally
  • Thromboembolic Disease
  • Too much hemostasis
  • Natural anticoagulants are missing
  • Or Fibrinolytics are missing

5
Signs of Bleeding
  • Primary hemostasis small vessel hemorrhage
  • Immediate bleeding
  • Petechiae (except vWDz) - lt3 mm
  • Ecchymoses
  • Bleeding from surfaces
  • Nose, mouth
  • Ocular - hyphema
  • GI hematemesis, melena, hematochezia, hematuria
  • repro
  • Prolonged bleeding after injury or surgery

6
Signs of Bleeding
  • Secondary hemostasis
  • Delayed bleeding after injury or surgery
  • Bleeding into cavities
  • Joints, pleural space, abdomen
  • CNS
  • Muscular hematomas
  • Hemoptysis can present as melena
  • Blood coughed up, swallowed and digested
  • Both primary and secondary
  • Epistaxis
  • Ecchymoses
  • If severe 1o and 2o bleeding types blend

7
Assessment of Coagulation
  • Is bleeding appropriate to injury?
  • Control arterial bleeding with ligation
  • If not, assess coag status ASAP
  • Platelet count
  • PT, PTT/ACT
  • BMBT
  • FDPs, D-dimers
  • Factor assays

8
Coagulation Tests
  • Primary hemostasis
  • Platelet estimate
  • Count platelets in 10 HPF (oil)
  • Divide by 10 to get average
  • Multiply by 15-20,000
  • 8-15 platelets/HPF is adequate
  • Automated platelet count
  • Look at the feathered edge for platelet clumping
    (cats!!)
  • If clumping, get a new sample
  • Use citrate (blue top) and count immediately

9
Coagulation Tests
  • Primary hemostasis
  • MPV Mean Platelet Volume
  • Increased in dogs when immature platelets in
    circulation
  • Indicates increased platelet pdxn
  • DIC, vasculitis, chronic hemorrhage
  • Decreased with IMT - 50
  • Large, bizarre platelets
  • Otter hound thrombocytopathia
  • Cats with myeloproliferative disease

10
Coagulation Tests
  • Primary hemostasis
  • Platelet function tests
  • Academia
  • Must be performed within 2-3 hours of blood
    collection

11
Coagulation Tests
  • Primary hemostasis
  • Buccal mucosal Bleeding Time (BMBT)
  • Assesses primary hemostasis
  • Prolonged if platelets lt20,000/ul
  • Rebleeding can indicate problems with secondary
    hemostasis
  • The only in clinic test that evaluates vessel and
    platelet function
  • Screen for vWDz in likely suspects
  • Reasonable pre-operative estimate of likelihood
    of surgical hemorrhage, if you check for
    rebleeding

12
Coagulation Tests
  • Primary hemostasis
  • How severe must Tpenia to cause spontaneous
    bleeding?
  • Can happen lt50,000/ul
  • More often lt20,000/ul
  • Splenomegaly of any kind can result in
    thrombocytopenia
  • Platelets sequestered in the spleen, liver or
    lymph nodes

13
Coagulation Pathway
14
Coagulation Pathway
15
Coagulation Pathway
16
Coagulation Tests
  • Secondary hemostasis
  • Partial thromboplastin time (PTT)
  • Intrinsic and common pathways
  • Heparin acts on intrinsic pathway
  • Prothrombin time (PT)
  • Extrinsic and common pathways
  • PIVKA is a form of PT test
  • PIVKA is not specific for rodenticide toxicity
  • Factor 7 deficiency
  • Common pathway - DIC, liver failure
  • No clinical significance when PT/PTT are shorter
    than normal
  • PT lt3 sec and PTT lt5 sec prolonged may not be
    clinically significant

17
Coagulation Tests
  • Secondary hemostasis
  • Activated clotting time (ACT)
  • Less sensitive version of PTT
  • Intrinsic and common pathways
  • Platelets as well
  • Thrombocytopenia can elevate ACT by lt10
  • No such platelet effect on PTT
  • Factors must be 5 of normal for ACT to be
    elevated
  • If ACT is increased, things are really bad

18
Coagulation Tests
  • Secondary hemostasis
  • Thrombin time (TT)
  • Assesses fibrinogen activity
  • Part of common pathway

19
Coagulation Tests
  • Fibrinolysis
  • Fibrin degradation products (FDPs)
  • AKA FSPs fibrin split products
  • Measure fibrinolysis
  • High with clot formation and breakdown over time
  • DIC
  • Chronic bleeding
  • Hypercoagulable state
  • Neoplasia
  • Cushings Disease
  • PLN, PLE
  • IMHA

20
Coagulation Tests
  • Fibrinolysis
  • D-dimers
  • Measure fibrinolysis
  • More specific for DIC than FDPs
  • Normal D-dimers exclude DIC as a diagnosis with
    99.5 confidence level

21
Anticoagulants
  • Antithrombin III
  • Produced by the liver
  • Activated by heparin
  • Modulates excessive coagulation
  • Consumed by coagulation
  • Lost with albumin PLN, PLE
  • Protein C (vitamin K dependent)
  • Protein S (vitamin K dependent)
  • TFPI Tissue Factor Pathway Inhibitor

22
Coagulation Pathway THATS Not ALL!!
23
Fibrinolysis
  • tPA tissue Plasminogen activator converts
    plasminogen within the clot to plasmin
  • Plasmin breaks down fibrin clot
  • So tPA promotes fibrinolysis, so that clots are
    only temporary
  • Urokinase and streptokinase work similarly
  • tPA, urokinase and streptokinase are the clot
    busters

24
Excessive Fibrinolysis
  • Enzymes prevent excessive fibrinolysis which
    would lead to rebleeding
  • They break down the clot busters
  • Alpha2-antiplasmin
  • inactivates plasmin
  • PA1-I tPA-inhibitor1
  • Inactivates tPA and uPA
  • uPA urokinase plasminogen activator
  • FDPs and d-Dimers inhibit the coagulation cascade
    by negative feedback

25
Coags in Practice
  • Why do them at all???
  • Patient shows signs of coagulopathy
  • Excessive bleeding
  • thrombosis
  • Presurgical evaluation
  • Patient predisposed to coagulopathy
  • Procedure increases risk of bleeding
  • Rodenticide toxicity suspected
  • DIC suspected
  • Genetic screening for breeding
  • No expensive equipment for platelet count, ACT,
    BMBT
  • Can send out the rest

26
Coags in Practice
  • Platelet count
  • Partial thromboplastin time (PTT)
  • Prothrombin time (PT)
  • Reference lab
  • Human hospitals often
  • not calibrated for animals (Pluto)
  • Synbiotics SCA 2000
  • 2000-3000
  • Idexx Coag Dx

27
Coags in Practice
  • Activated clotting time
  • Reference labs
  • Gray top tubes (other colors now)
  • Diatomaceous earth (DE) or kaolin
  • http//www.haemtech.com/ACT.htm
  • Warming block or hand heat
  • 2 ml whole blood in the tube immediately
  • Invert once every 15-30 seconds
  • First clot is the ACT
  • Normal less than 2 minutes
  • SCA 2000
  • HESKA i-STAT

28
Coags in Practice
29
Coags in Practice
30
Coags in Practice
31
Coags in Practice
  • Buccal Mucosal Bleeding Time (BMBT)
  • Simplate, Triplett, Surgicutt device
  • Lift the upper lip (gauze muzzle)
  • Remove the device safety tab
  • Place the device on the mucosa
  • Push the device trigger button
  • Dab dripping blood
  • every 15 seconds,
  • but dont touch
  • the clot

32
Coags in Practice
  • Buccal Mucosal Bleeding Time (BMBT)
  • When bleeding stops, you have BMBT
  • Normal is 2-4 minutes
  • 5 minutes isnt worrisome
  • Check the patient in 10-15 minutes for rebleeding
  • DONT DO BMBT IF
  • Platelets lt40,000/ul
  • Petechiae are present
  • ACT is increased

33
Coags in Practice
  • EVERY PRACTICE can have in house PLATELET COUNT,
    ACT BMBT
  • EVERY PRACTICE can use a lab for the rest

34
Coags in Practice
  • Tips for coag test sample handling
  • Take blood from a peripheral vein
  • Avoid cystocentesis if coagulopathy
  • Holding the vein off for too long can lead to
    platelet fibrinolysis activation
  • Multiple sticks can lead to the same you want a
    clean first stick.
  • If you dont get blood quickly, move to another
    vein.
  • Hemolysis and severe lipemia can prevent accurate
    results

35
Coags in Practice
  • Tips for coag test sample handling
  • 1 citrate9 blood
  • Vacuum tubes should autodraw
  • Run platelet count immediately
  • Run tests on whole citrated blood within 2 hours
  • Centrifuge promptly to harvest plasma for outside
    lab tests
  • Freeze immediately in plastic or siliconized
    glass tubes
  • Ship frozen on dry ice
  • May need special blue top clot tubes for FDPs
    ask lab

36
Coagulopathies - DDx
  • Disorders of primary hemostasis
  • thrombocytopenia
  • thrombocytopathia
  • Von Willebrand Disease
  • vasculitis
  • Disorders of secondary hemostasis
  • Congenital factor deficiencies
  • Liver disease (poor pdxn)
  • Vitamin K antagonism
  • Snake bite envenomation
  • Disorders of both
  • Consumption DIC, massive hemorrhage
  • Paraneoplastic coagulopathy

37
Thrombocytopenia - DDx
  • Bone marrow disease lack of production
  • Consumption
  • DIC
  • Massive hemorrhage
  • Destruction
  • immune mediated
  • Sequestration
  • Splenomegaly
  • Hepatomegaly
  • Lymphadenitis, lymphangitis
  • vasculitis

38
Thrombocytopenia - DDx
  • Infectious Diseases
  • Multiple causes
  • Viruses
  • Canine CDV, CHV, CPV, CAV2
  • Feline FeLV, FIV, panleukopenia, FIP
  • Arthropod-Borne
  • Ehrlichia spp.
  • Babesia spp.
  • Heamobartonella spp.
  • Arthropod-Borne
  • Rickettsia spp.
  • Leishmania spp.
  • Cytauxzoon spp.
  • Borrelia spp.
  • Bacterial
  • Sepsis
  • Borrelia spp.
  • Leptospira spp.
  • Fungal
  • Histoplasma spp.
  • Candida spp.

39
Thrombocytopenia - DDx
  • Neoplasia
  • Multiple causes
  • Marrow suppression
  • Metastatic disease
  • Hematopoietic neoplasia
  • Lymphoma
  • Multiple myeloma
  • leukemias
  • DIC
  • Hemangiosarcoma
  • Inflammatory mammary carcinoma
  • Vasculitis
  • Cytotoxic drug therapy
  • Azathioprine
  • Chlorambucil
  • Cyclophosphamide
  • Doxorubicin

40
Thrombocytopenia - DDx
  • Drug Therapy
  • Multiple causes
  • Impaired platelet pdxn
  • Immune destruction
  • Platelet dysfunction
  • Antibiotics
  • Penicillin
  • Chloramphenicol
  • Sulfonamides
  • Antifungals
  • NSAIDs
  • Ibuprofen
  • Cardiopulmonary drugs
  • Procainamide
  • Cytotoxic drugs
  • Azathioprine
  • Chlorambucil
  • Cyclophosphamide
  • Doxorubicin
  • Estrogen
  • Methimazole

41
Immune Mediated Thrombocytopenia
  • Primary autoimmune
  • Very rare in cats
  • Dog breeds predisposed
  • Same as IMHA
  • Cocker spaniel
  • Poodle
  • Old English Sheepdog
  • Diagnosis of exclusion
  • Rule out other causes of Tpenia (normal coags,
    normal BMBT unless lt5K platelets)
  • Rule out causes of secondary IMT
  • Platelets lt50,000/ul
  • Increased megakaryocytes in the marrow
  • Response to immunosuppressive therapy

42
Immune Mediated Thrombocytopenia
  • Secondary same as for IMHA
  • infection
  • Drug therapy
  • Paraneoplastic
  • transfusion
  • Anti-platelet antibodies
  • Doesnt distinguish between 1o 2o IMT
  • Sensitive for IMT
  • But not very specific (many false negatives)
  • Low MPV microthrombocytosis
  • MPV lt 5.5 fL platelets lt20,000/ul is almost
    always IMT (primary or secondary)
  • But only 50 of dogs with IMT have this
    combination of abnormalities

43
Breed Specific Thrombocytopenia
  • Greyhounds
  • Normal platelet count 150,00/ul
  • Coags normal
  • Remember greyhounds also predisposed to von
    Willebrand Disease and Babesia
  • Cavalier King Charles Spaniel
  • Normal coags
  • Normal platelets 25,000/ul-100,000/ul
  • Giant platelets on blood smear
  • CBC machines wont count them
  • Platelet mass usually normal
  • Platelet mass Platelet count x MPV
  • Causes no clinical problems

44
Thrombocytopathia
  • Platelet dysfunction
  • hereditary
  • acquired
  • Acquired Thrombocytopathia
  • Drugs
  • Disease
  • Anemia
  • Liver failure (plus factor deficiency)
  • Uremia (plus vasculitis)
  • DIC (plus consumptive coagulopathy)
  • Paraproteinemia
  • Monoclonal gammopathy
  • Ehrlichia, plasma cell myeloma

45
Thrombocytopathia - DDx
  • Drug Therapy
  • Antibiotics
  • Beta lactams
  • Carbenicillin
  • cephalosporins
  • Antifungals
  • NSAIDs
  • Aspirin
  • Phenylbutazone
  • Ibuprofen
  • Naproxen
  • Cardiopulmonary drugs
  • Aminophylline
  • Verapamil
  • Diltiazem
  • Isoproterenol
  • Propranolol
  • Dextran
  • Phenothiazines
  • CAUTION in pets with thrombocytopenia, undergoing
    surgery or signs of coagulopathy

46
Thrombocytopathia
  • Hereditary Thrombocytopathia
  • Likely underdiagnosed
  • Otter hound, Great Pyrenees thrombasthenia
  • Basset hound, Spitz
  • Persian cat Chediak-Higashi
  • Cocker spaniel
  • Collie cyclic neutropenia (stem cell defect)
  • Boxer
  • German shepherd
  • Consider BMBT prior to major surgery

47
von Willebrand Disease
  • Most common canine hereditary coagulopathy in
    dogs
  • Does not occur in cats
  • Clinical signs of primary hemostasis defect
  • Mucosal hemorrhage, prolonged bleeding after
    injury
  • Petechiae are rare
  • (Indy)
  • von Willebrand Factor is not a coagulation factor
  • Made by the endothelium
  • Acts as carrier protein for factor 8
  • Severe vWDz can cause result in bleeding due to
    lack of secondary hemostasis

48
von Willebrand Disease
  • Three subtypes of vWDz
  • Type 1 vWDz most common complex genetics
  • Mild to moderate bleeding
  • Low plasma vWAg, normal multimer distribution
  • Type 2 vWDz simple recessive
  • Moderate to severe bleeding
  • Low vWAg, loss of high MW multimers
  • Type 3 vWDz simple recessive
  • Severe bleeding
  • Total lack of vWF

49
von Willebrand Disease
  • Diagnosis
  • Platelet count
  • Normal (may be mildly low if hypothyroid)
  • PT, PTT/ACT
  • Normal (increased of Type 3)
  • BMBT
  • Type 1 5-12 minutes
  • Type 23 gt12 minutes
  • vWFAg assay
  • carriers 35-65
  • Type 1 5-30 (clinical lt15)
  • Type 2 1-5, no high MW multimers
  • Type 3 lt0.1

50
von Willebrand Disease
  • Type 1 - mild
  • Airedale
  • Akita
  • Dachshund
  • Doberman
  • German shepherd
  • Golden retriever
  • Greyhound
  • Irish wolfhound
  • Manchester terrier
  • Pembroke Corgi
  • Poodle
  • Schnauzer
  • Sheltie

Type 2 - moderate German shorthair pointer German
wirehair pointer
Type 3 - severe Chesapeake Bay Retriever Dutch
kooiker Scottish terrier Sheltie Less
commonly Cocker spaniel Spitz Labrador
retriever Pit bull terrier Rottweiler
DNA Tests available for some breeds
51
Vasculitis Clinical Signs
  • Peripheral edema (dependent)
  • Proteinuria
  • Exudative skin lesions
  • Ascites, pleural/pericardial effusion
  • Necrosis of extremities
  • Nose
  • Ear tips
  • Nail beds toes
  • Tail tip
  • hypoalbuminemia

52
Vasculitis - DDx
  • Systemic inflammation
  • Infection
  • Bacterial sepsis, Lepto, endocarditis,
    pyelonephritis, pyometra, prostatitis, abscess
  • Viral - FIP
  • Fungal systemic infection
  • Parasitic heartworm Dz, rickettsiae
  • Immune mediated
  • Primary autoimmune
  • neoplasia
  • Uremia
  • Infection of the blood vessels
  • Rocky Mountain Spotted Fever
  • Ehrlichia spp.

53
Vasculitis Work-Up
  • CBC, panel, lytes, UA
  • Urine PC ratio if proteinuria on dipstick
  • Urine culture if dilute urine
  • Anti-platelet-Ab if platelets lt50,000/ul
  • FeLV/FIV in cats, HWAg in dogs
  • Chest x-rays
  • Echo if murmur
  • Blood culture if endocarditis
  • Abdominal x-rays and/or ultrasound
  • Tick panel - RMSF, Ehrlichia, Borrelia
  • ANA
  • Definitive diagnosis of elusive vasculitis is by
    skin biopsy

54
Vasculitis Coags
  • Platelet count
  • lt150,000/ul
  • May see E platys in platelets, or morulae from
    other species in WBC
  • PT, PTT/ACT
  • Normal
  • ACT may be lt10 prolonged if thrombocytopenia
  • BMBT
  • Prolonged

55
Thrombocytosis
  • Falsely increased platelets
  • Lipid droplets in lipemic animals
  • Small RBC iron deficiency anemia
  • Schistocytes
  • IMHA
  • DIC
  • RBC fragility congenital, liver disease
  • Zinc toxicity
  • Iron deficiency anemia
  • Microangiopathy
  • Sharp spikes on the platelet histogram and low
    MPV make you suspect this

56
Coagulation Pathway - Hemophilia
57
Hemophilia
  • See the chart
  • Hemophilia A (Factor 8) and B (factor 9) are sex
    linked recessives
  • Most affected individuals are male
  • Factor must be lt5 for spontaneous bleeding
  • Secondary hemostatic defects
  • Delayed bleeding, into cavities
  • Often evident at a very young age
  • Bleeding out from umbilicus
  • Almost always evident prior to 2-3 years

58
Hemophilia
  • Factor 7 deficiency
  • increased PT and normal PTT
  • Factor 10 deficiency
  • increased PT and PTT
  • Most of the rest increased PTT and normal PT
  • Factor 11 and 12 (Hageman) deficiencies rarely
    cause clinical bleeding
  • There is a deficiency of all vitamin K dependent
    factors in the Devon Rex
  • 2, 7, 9, 10
  • Causes severe bleeding
  • Increased PT and PTT
  • Long term vitamin K Tx can normalize
  • Cockers and Kerry Blues can have prothrombin
    deficiency
  • Common pathway increased PT, PTT/ACT, TT

59
Hemophilia
  • Factor assays are diagnostic (Cornell)
  • http//ahdc.vet.cornell.edu/coag/test/
  • Coag panels
  • individual tests
  • Submission form
  • DNA Tests are available fro some defects in some
    breeds
  • www.vetgen.com
  • www.dog-dna.com
  • www.healthgene.com
  • www.optigen.com

60
Hemophilia
61
Vitamin K Antagonism
62
Vitamin K Antagonism
  • Vitamin K1 found in green leafy vegetables
  • phytonadione
  • Vitamin K3 is found in drugs
  • menadione
  • Causes of Vitamin K deficiency
  • Neonate born to malnourished mother
  • Severe bacterial deficiency in ileum
  • Decreased vitamin K absorption
  • Bile duct obstruction
  • Exocrine pancreatic insufficiency
  • Lymphangiectasia
  • Rodenticide toxicity is by far most common

63
Vitamin K Antagonism
  • Disorder of secondary hemostasis
  • Delayed bleeding, into cavities
  • Signs begin 2-5 days after ingestion

64
Vitamin K Antagonism
  • Diagnosis
  • platelets
  • Decreased if prolonged bleeding
  • Usually ingested at least 3-4 days before
  • PT elevated first for 12 hours or less
  • Some say PIVKA elevated before PT
  • PIVKA procoagulant Proteins Induced by Vitamin
    K Antagonism
  • then PTT within 12-24 hours, then ACT
  • FDPs and d-Dimers could be elevated with chronic
    bleeding
  • TT should be normal
  • Send anticoagulant toxicology screen out
  • Vitamin K therapy will not affect results

65
Vitamin K Antagonism
  • 1st Generation
  • Coumadin
  • Warfarin
  • Pindone
  • Shorter half life

2nd Generation Bromadiolone Brodifacoum Diphacinon
e Longer half life Lower incidence of drug
resistance
3rd Generation Others Longest half life
66
Heparin Toxicity
  • Causes
  • Iatrogenic
  • Mast cell tumor degranulation
  • Heparin prolongs PTT gt PT
  • Monitor PTT for heparin therapy for
    thromboembolic disease
  • INR is an even better monitor for coumadin
    therapy
  • International Normalization ratio

67
Liver Failure
  • Define liver failure
  • Significantly elevated bile acids
  • Cant be explained by prehepatic or posthepatic
    icterus
  • Prehepatic icterus (hemolysis)
  • Posthepatic icterus (biliary obstruction)
  • More than half of liver failure patients have at
    least one abnormal coag test
  • Only 2 of liver patients develop hemorrhage
  • Concurrent coagulopathies
  • Biliary obstruction can cause vit K deficiency
  • DIC
  • Disorder of secondary hemostasis

68
Liver Failure
  • Diagnosis of coagulopathy due to liver failure
  • Blood film
  • Acanthocytes
  • Target cells leptocytes codocytes

69
Liver Failure
  • Diagnosis of coagulopathy due to liver failure
  • Blood film
  • Acanthocytes
  • Target cells leptocytes codocytes
  • Factor Assays
  • Some say PIVKA most sensitive indicator for risk
    of hemorrhage due to liver failure
  • PT and PTT elevated
  • ACT elevated if severe
  • BMBT
  • Normal, then rebleeding if severe
  • AT3, TT
  • AT3 low, TT prolonged

70
Paraneoplastic Coagulopathy
  • Thrombosis
  • Iatrogenic
  • Mast cell tumor degranulation
  • Hemorrhage
  • Thrombocytopenia
  • inflammatory activation of platelets
  • Microangiopathy
  • Secondary IMT
  • Chemotherapy induced bone marrow suppression
  • Thrombocytopathia
  • DIC HAS and inflammatory MGC
  • Disruption of blood vessels by tumor invasion

71
Paraneoplastic Coagulopathy
  • 2/3 of dogs with MGT have at least one abnormal
    coag test
  • Dogs with stage III or IV cancer are more likely
    to have coagulopathy
  • 83 of dogs taking chemo have at least one
    abnormal coag test
  • Only 20 of cats with neoplasia have coaguloapthy
  • LSA and HSA are commonly associated with
    coagulopathy.

72
Chemo Drugs Affecting Coagulation
  • Marrow Suppression
  • CCNU
  • doxorubicin
  • Bleomycin
  • Cytosine arabinoside
  • Melphalan
  • Methotrexate
  • Cisplatin, carboplatin
  • Actinomycin D
  • Thrombocytosis
  • Vincristine, vinblastine
  • Thrombocytopathia
  • Melphalan
  • vincristine
  • Factor Pdxn Suppression
  • L-asparaginase
  • Vitamin K Antagonism
  • Actinomycin D
  • Dysfibrinogenemia
  • Melphalan
  • Increased fibrin
  • Doxorubicin
  • Daunorubicin

73
Snake Bite Coagulopathy
  • Cause
  • Toxins in the snake venom affect coagulation in
    many ways
  • The most common affect is lack of fibrin
  • Lack of secondary hemostasis, though bleeding is
    rare
  • The Mojave rattler causes no coagulopathy
  • Diagnosis
  • Locate the snake bite injury
  • Decreased platelets
  • Prolonged PTT, PTT, ACT
  • Low fibrinogen
  • Elevated FDPs
  • d-dimers often normal
  • True DIC can occur if toxicity is severe

74
Thrombocytosis
  • gt 800,000-900,000/ul platelets
  • DDx
  • Chronic blood loss
  • Paraneoplastic
  • Systemic inflammation
  • Primary bone marrow disease
  • Cushings Disease
  • Post-splenectomy
  • Work-up (after CBC, panel, UA)
  • Endoscopy, chest x-rays, abdominal US, abdominal
    x-rays, fecal cytology

75
Thrombosis
  • Hypercoagulable states
  • IMHA
  • 80 of dogs who died of IMHA had evidence of
    thromboembolic disease on necropsy
  • Hyperadrenocorticism
  • Protein losing enteropathy and nephropathy
  • AT3 is similar size as albumin
  • AT3 level is a good assessment for risk of
    thrombosis
  • AT3 60-75 at risk)
  • AT3 lt60 - grave prognosis
  • Systemic amyloidosis
  • Canine parvovirus
  • Neoplasia 30 have PTE

76
Thrombosis
  • Symptoms of Thromboembolism
  • Caused by ischemia of the organ affected
  • PTE pulmonary thromboembolism
  • Acute dyspnea
  • Renal artery
  • Acute renal failure
  • Jugular vein
  • Swelling of the head
  • Diagnosis
  • Doppler ultrasound
  • Angiography, venography
  • Nuclear scans

77
Disseminated Intravascular Coagulopathy (DIC)
  • End result of systemic thrombosis
  • Rarely recognized in cats
  • Always secondary disease
  • Cause
  • Any conditions of increased coagulation
  • Systemic inflammation triggering thrombosis
  • Hyperthermia is one of the causes that might have
    a more favorable prognosis
  • Two flavors
  • Acute and uncompensated
  • Chronic and compensated

78
Disseminated Intravascular Coagulopathy (DIC)
  • Blood film
  • Schistocytes (10 of the time)
  • Platelet count
  • lt150,000/UL
  • Partial thromboplastin time (PTT)
  • prolonged
  • Prothrombin time (PT)
  • Prolonged
  • Activated clotting time (ACT)
  • Prolonged if severe

79
Disseminated Intravascular Coagulopathy (DIC)
  • Fibrin degradation products (FDPs)
  • increased
  • D-dimers
  • increased
  • Antithrombin III
  • Decreased (lt75)
  • Thrombin Time
  • prolonged
  • Fibrinogen
  • decreased

80
Ecchymoses/Petechiae Algorithm
Platelet count
Both prolonged
Low (next slide)
Normal or increased
FDPs, TT, AT3
PT, PTT/ACT
normal
  • VitK deficiency
  • All normal
  • Liver Failure
  • TT prolonged
  • AT3 low
  • Factor 10 deficiency
  • All normal blood to Cornell
  • prothrombin deficiency
  • TT prolonged
  • Snake Bite
  • FDP increased
  • TT prolonged
  • AT3 normal
  • Chronic Bleeding
  • FDPs increased

One prolonged
BMBT
  • PT congenital def. 7
  • early antiVitK
  • PTT congen def 8 9 11 12
  • severe vWDz - 8
  • heparin toxicity

normal
prolonged
Observe Work up vasculitis
vWF assays Work up vasculitis platelet function
Factor assays to Cornell vWF assays Rodenticide
tox screen or treat with VitK Check for MCT
vasculitis or problem resolving
vWDz Vasculitis thrombopathia
81
Ecchymoses/Petechiae Algorithm
low platelet count
PT, PTT/ACT
normal
Both prolonged
50-150,000/ul
lt50,000/ul
FDPs, D-dimers, TT
ACT lt 10 sec prolonged
BMBT
bone marrow
  • Severe bleeding platelet consumption
  • Advanced Vitamin K deficiency
  • DIC
  • Increased FDPs, D-dimers, TT
  • Snake Bite
  • Increased FDPs, TT

Severe platelet problem
normal
prolonged
neoplasia rickettsial dz Aplasia Infection toxicit
y
platelet clumps hyperlipidemia Cavalier mild
vasculitis mild rickettsial
Vasculitis rickettsial dz Some thrombocyto-pathias
FDPs elevated
normal
Hypercoagulable state
1o or 2o IMT
82
Ecchymoses/Petechiae Algorithm
FDPs elevated Platelets, PT, PTT, ACT, BMBT,
D-dimers, TT, AT3 normal
Hypercoagulable state
  • Remember..
  • Some animals will have multiple coagulopathies
    simultaneously
  • DIC
  • Hypercoagulation
  • Severe bleeding
  • Vasculitis
  • IMT

83
Epistaxis Algorithm
Onset
history of nasal discharge
acute onset
History of trauma?
serosanguinous to mucopurulent
hemorrhagic
yes
no
check out local processes
supportive and symptomatic care, surgical repair
check blood pressure and go to petechia-ecchymoses
algorithm
normal
normal
84
Epistaxis Local Processes
  • DDx
  • Nasal foreign body
  • Inhalation
  • Reflux into caudal nasopharynx
  • Infection
  • Chronic allergic rhinitis leading to 2o bacterial
  • Fungal
  • Viral
  • Parasites - Nasal mites, Cuterebra, Capillaria
  • Rickettsial infection
  • Nasopharyngeal polyps
  • Aneurysm or ruptured AV fistula

85
Epistaxis Local Processes
  • DDx
  • Neoplasia
  • TVT
  • Young animals
  • Adenocarcinoma
  • Sarcoma melanoSA, chondroSA, fibroSA
  • Lymphoma
  • cats gtdogs
  • Young animals
  • Dental disease
  • Tooth root abscess
  • Oronasal fistula

86
Epistaxis Local Processes
  • Other signs of nasal disease
  • Sneezing
  • Reverse sneezing
  • Gagging caudal nasopharynx
  • Pawing at face rostral nasal cavities
  • Melena, hemoptysis
  • Bilateral epistaxis
  • Check out coagulopathy first
  • Neoplasia can begin on one side, invade the
    septum and eventually affect both sides

87
Epistaxis Work Up
  • CBC
  • Iron deficiency anemia
  • thrombocytopenia
  • Profile
  • Panhypoproteinemia indicates blood loss
  • High globulins indicate chronic inflammation
  • Neoplasia
  • Chronic rhinitis
  • Chronic infection fungal, viral, bacterial,
    rickettsial
  • Renal disease, Hepatic disease
  • Hyperadrenocorticism hypertension
  • Triglycerides - hyperviscosity
  • Cats - FeLV/FIV Dogs heartworm test

88
Epistaxis Work Up
  • UA
  • Proteinuria PLN, hypertension
  • Confirm with urine proteincreatinine ratio
  • Coags
  • PT, PTT/ACT high
  • Tests for DIC FDPs, D-dimers, ATIII
  • Factor Assays
  • Normal PT/PTT, prolonged BMBT
  • vWF Assays
  • Platelet function tests
  • Look for causes of vasculitis
  • Blood pressure if high
  • T4/Free T4 in cats

89
Epistaxis Work Up
  • Imaging
  • Chest x-rays
  • Hemoptysis can present as epistaxis
  • Nasal x-rays under sedation
  • Dental x-rays if indicated
  • CT is nice
  • Nasal flush, rhinoscopy and biopsies
  • Only if coagulopathy has been ruled out
  • Culture is rarely helpful
  • Exploratory rhinotomy if all else fails

90
Epistaxis Supportive Care
  • Ice packs
  • Intranasal epinephrine
  • Cage rest
  • If coagulopathy or severe bleeding, transfusion
    may be necessary
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