Disorders of hemostasis in small animals

Hemostasis definition

Stopping the flow of blood

Reduced hemostasis results in what?

Bleeding

Increased hemostasis results in what?

Thrombosis

Primary hemostasis problems center around what part of the clotting process?

Formation of the platelet plug

Secondary hemostasis problems center around what part of the clotting process?

Stabilization of the platelet plug

Tertiary hemostasis problems center around what part of the clotting process?

Breakdown of the platelet plug

Primary hemostasis problems can result from disorders of what cellular factors?

Vascular endothelium, platelets, von Willerbrand factor

Secondary hemostasis problems can result from disorders of what cellular factors?

Fibrin formation, coagulation proteins/factors, intrinsic and extrinsic clotting cascades

Tertiary hemostasis problems can result from disorders of what cellular factors?

Fibrinolysis, Plasmin

What bleeding disorders impact the primary hemostasis step?

Thrombocytopenia, thrombocytopathia, Von Willerbrand’s Disease, Vasculopathies

What bleeding disorders impact the secondary hemostasis step?

Anticoagulant rodenticide toxicity, liver failure, congenital factor deficiencies (hemophilia for example)

What bleeding disorders impact the tertiary hemostasis step?

Hyperfibrinolysis

What are complex or “mixed” disorders involving multiple aspects of hemostasis?

Disseminated intravascular coagulation, angiostrongylus vasorum infection, sepsis, trauma associated coagulopathy

Thrombocytopenia is often associated with what clinical signs?

Petechiation and ecchymoses, epistaxis, GI bleeding (may result in melaena), Signs associated with hemorrhagic anemia thrombocytopenia may also be noted on hematology

Von Willerbrand’s disease is often associated with what clinical signs?

Prolonged bleeding at surgical sites, prolonged bleeding at estrus, other signs associated with hemorrhagic anemia

Coagulopathies are often associated with what clinical signs?

Hematoma formation, hemarthrosis, pulmonary hemorrhage, bleeding into body cavities, other signs associated with hemorrhagic anemia

What laboratory assessments can determine a problem in the primary hemostasis phase?

Platelet count, buccal mucosal bleeding time

What laboratory assessments can determine a problem in the secondary hemostasis phase?

Prothrombin time, activated partial thromboplastin time, Fibrinogen

What laboratory assessments can determine a problem in the tertiary hemostasis phase?

Fibrin-degradation products FDPs, D-dimers, TEG/ROTEM

What platelet counts are considered concerning (RI 200-500)?

<50 × 10^9/l

What is considered an adequate platelet count per x100 high power field?

10-15

Buccal mucosal bleeding time is used to assess what?

Platelet funciton, vascular response to injury, adequacy of vWF

Why should you do a platelet count before performing a buccal mucosal bleeding time?

Thrombocytopenia will also result in prolonged times and easier to check!

When should buccal mucosal bleeding cease?

2-4 min

What breeds are predisposed to congenital bleeding disorders?

German Shepherd Dogs, Doberman Pinschers

Why would a patients deworming history be prevalent in a bleeding disorder presentation?

Angiostrongylus vasorum for example

What tests can be used to evaluate secondary hemostasis?

Standard Coagulation tests: Prothrombin time and activated partial thromboplastin time

Prothrombin time test can show disorders in what factors/components of clotting?

Extrinsic and Common pathways, Factor VII

Activated partial thromboplastin time testing can show disorders in what factors/components of clotting?

Intrinsic and common pathway, Factors IX and VIII

Platelet count of <30 × 10^9/l is associated with what?

Spontaneous bleeding

Why have we moved away from activated clotting time tests?

Clotting factors have to be very low before the time is prolonged, test lacks sensitivity

Laboratory only evaluation of tertiary hemostasis tests include

D-dimers and Fibrin degredation products

What are potential causes of epistaxis?

Hemostatic disorders, nasal tumors, aspergillosis, nasal foreign body, hypertension

What are potential causes of hemoabdomen?

Hemostatic disorder, trauma, neoplasia (splenic, hepatic, or vena cava involvement)

What bleeding disorders are acquired disorders?

Thrombocytopenia, thrombocytopathia, vasculopathies, anticoagulant rodenticide toxicity, liver failure, hyperfibrinolysis

What is the most common cause of thrombocytopenia?

Immune mediated thrombocytopenia

If you suspect bone amrrow failure, what tests should be done?

Look for other cytopenias, perform bone marrow evaluation

What test/result will lead you to consider a patient ahs an increased consumption (ex severe blood loss)?

Changes on coagulation profile

What is the average signalment of immune mediated thrombocytopenia?

Median age of 4-5 years, Cocker Spaniels seem predisposed

What are the presenting signs of immune mediated thrombocytopenia?

Primary hemostatic disorder, ex surface/capillary bleeding

How do we diagnose immune mediated thrombocytopenia?

Very low platelets, demonstration of thrombocytopenia, diagnosis of exclusion → this diagnosis

How should we manage an immune-mediated thrombocytopenic patient?

Gentle handling, blood transfusion if severely anemic, treat underlying trigger if applicable, immunosuppression, offer vincristine

What can vincristine doe for our bleeding disorder patients?

Increases number of circulating platelets (in an effort to reduce hospitalization times)

How do anticoagulant rodenticides lead to bleeding disorders?

They inhibit Vit K recycling → reduced active clotting factors II, VII, IX, and X

How do we diagnose anticoagulant rodenticide toxicity?

History of potential exposure within preceding 2-3 days, signs compatible with coagulopathy (ex bleeding into body cavities, hematomas)

Frequently present with signs of blood loss, anemia and/or hypovolemia

What lab tests can help diagnose anticoagulant rodenticide toxicity?

prolonged PT and aPPT, reduced platelet count, anemia (pre regenerative or regenerative)

What is the treatment for anticoagulant rodenticide toxicity if ingestion is known to be <6 hours ago?

Emesis, decontamination, monitor PT up to 48 h post ingestion

What is the treatment for anticoagulant rodenticide toxicity if patient is presenting with clinical signs?

SQ Vit K1 for 24-48 hours if bleeding, then oral

Supportive care: Thoracocentesis only if dyspneic from pleural effusion, Transfusion of whole blood if severe anemia, Fresh frozen plasma to replace factors

How can severe/chronic liver disease lead to hematological conditions?

Cholestasis → failure of Vit K absorption → clotting disorders

How does end-stage liver disease lead to hematologic disorders?

Reduced production of clotting factors

AND

Reduced activation of vit K dependent factors

What are clinical signs of liver disease?

Coagulopathy: expect cavity bleeds

Spontaneous bleeding uncommon except in fulminant acute liver failure

Increased bleeding risk with biopsy**

What lab test can aid diagnosis of liver disease as a cause of coagulopathy?

Prolongation of PT and aPTT, concurrent signs of liver/cholestatic disease

Including: Increased liver enzymes, increased bilirubin and/or bile acids, reduced albumin, reduced urea

What is the treatment for liver disease causing coagulopathies?

Supportive treatment for liver disease, Vit K supplementation prior to biopsy, Plasma to replenish coagulation factors

What cardiorespiratory signs can present from an angiostrongylus vasorum infection?

Cough, dyspnea, syncope, harsh lung sounds, exercise intolerance

What hemostatic signs can present from an angiostrongylus vasorum infection?

Epistaxis, conjunctival hemorrhage, prolonged surgical bleeding, bleeding into any body cavity, hemoptysis, petechiae/ecchymoses

What neurological signs can present from an angiostrongylus vasorum infection?

Paralysis, seizures, ataxia, weakness, proprioceptive deficits

How can we diagnose angiostrongylus vasorum infection?

Clinical presentation (including regional variations), tests of hemostasis including for low fibrinogen, thrombocytopenia, and prolonged PT and/or aPPT

Fecal Baermann’s test/fecal wet prep/ ELISA:IDEXX

Why may lab tests be normal in dogs that are actively bleeding?

Hyperfibrinolysis

How can we treat Angiostrongylus Vasorum infections?

Supportive care for hemorrhage, kill parasites, consider steroids

What licensed anthelmintics are capable of killing “lung worms?”

Imidacloprid/moxidectin and milbemycin

Why might steroids be used in lung worm infections?

For ‘worm kill’ effect, suppresses inflammatory/anaphylactic reactions as the worms die to other medications

How can we treat bleeding as a result of angiostrongylus vasorum infeciton?

Tranexamic Acid 

How does Tranexamic acid help control bleeding in lung worm infections?

Reduces activation of plasmin by binding to lysine receptors. End result is inhibiting fibrinolysis

What is Disseminated Intravascular Coagulation?

Widespread of activation of the coagulation pathway ins the presence of an underlying disease

Why does DIC occur?

Widespread endothelial damage/release of tissue thromboplastins secondary to neoplastic, inflammatory, or infectious disease and/or a variety of misc conditions

What are clinical signs of DIC?

Mixture of thrombosis and bleeding (compensated condition may not be associated with active hemorrhage)

How can we diagnose DIC?

Increased aPTT and/or PT, Thrombocytopenia (consumptive), decreased fibrinogen, increased FDPs and D-dimer

What is the prognosis for DIC?

Poor- hopeless

How can we treat DIC?

Eliminate the initiating cause, ensure adequate tissue perfusion, support target organs susceptible to microthrombi, ischemia or hemorrhage

Replacement of blood components

What is thrombocytopathia?

Platelet dysfunction - rare

When does thrombocytopathia occur?

Associated with an underlying disease process (infectious, systemic, drugs)

What diagnostic tests can be used to identify thrombocytopathia?

Normal PLT count, normal standard coagulation tests, prolonged BMBT, PFA/platelet aggregometry if available

How can we manage thrombocytopathia?

Supportive care, treat underlying disease if possible

What Bleeding disorders can be congenital?

Thrombocytopathia, Von Willerbrand’s disease, Congenital factor deficiencies, hyperfibrinolysis

What is Von Willerbrand’s disease?

Patients have a reduced concentration or function of ____ factors, breed dispositions

What clinical signs are seen in Von Willerbrand’s disease?

Excessive hemorrhage with trauma or surgery

How can we diagnose Von Willerbrand’s Disease?

Normal PLT and coagulation tests, Prolonged BMBT, testing for reduced vWF (<50%=affected)

How do we treat V W disease?

DDAVP (artificial factors) and cryoprecipitate. Palliative care

What clotting factor does Hemophilia A effect?

Factor VIII

What clotting factor does Hemophilia B effect?

Factor IX

What clotting factor does Hageman factor deficiency effect?

Factor XII

Clinical signs/presentations of clotting factor deficiencies all generally present how?

Variably

Features of Hemophilia A and B include

Prevalence in young <1yo animals, X linked recessive, prolonged aPTT, normal PT

Features of Hageman trait include

Cats, typically asymptomatic, prolonged aPTT, normal PT

What treatment can be used for inherited coagulation factor deficiencies?

Transfusion support

What is hyperfibrinolysis?

Excessive breakdown of fibrinogen, suspected cause for increased bleeding in greyhounds

How can we test for hyperfibrinolysis?

FDPs, D-dimers, TEG or ROTEM

How can we treat hyperfibrinolysis?

Supportive care ± transfusions

Tranexamic acid