Coagulopathies Flashcards
What is the main cause of vitamin K deficiencies? In large animals? What are 3 other possibilities?
- anticoagulant rodenticide containing Warfarin and other coumarins
- moldy sweet clover
- intestinal malabsorption
- bile duct obstruction
- liver failure
How does Warfarin cause coagulopathies?
blocks the carboxylase needed to alter vitamin K into its active form able to activate pre-factors II, VII, IX, and X
What are the 5 main clinical features of vitamin K deficiencies?
BLEEDING
- anemia, weakness, pallor
- hypovolemia, shock
- dyspnea due to bleeding into thoracic cavity
- lameness due to bleeding into joint cavities
- neurological signs due to bleeding into the brain
What are the 3 laboratory features of vitamin K deficiencies?
- regenerative anemia from hemorrhage
- variable leukogram
- normal platelet count, but may eventually develop reactive thrombocytosis
What are the expected values of RBC, PLT, MPV, PT, and PTT/AT for vitamin K deficiency? What value changes first? Why?
- anemia
- normal (vitamin K is necessary for coagulation, does not effet platelets)
- normal
- prolonged
- prolonged
PT —> factor VII has the shorted half-life
What are the expected values of RBC, PLT, MPV, PT, and PTT/AT? What value changes first? Why?
- anemia
- normal (vitamin K is necessary for coagulation, does not effect platelets)
- normal
- prolonged
- prolonged
PT —> factor VII has the shortest half-life
What should be considered in the differential diagnosis in a patient with suspicious history of rat poison exposure and only an increased PT?
Warfarin poisoning - PT will be the first prolonged/abnormal lab result because Factor VII has te shortest half-life (at this point, the animal may not show signs of bleeding)
What is disseminated intravascular coagulation (DIC)?
acquired syndrome characterized by intravascular activation of coagulation with loss of localization arising from different causes
ALWAYS secondary to some disease process activating the coagulation cascade
What are 6 possible causes of disseminated intravascular coagulation (DIC)?
- induction or exposure of tissue factor or other activators of coagulation due to sepsis, tissue necrosis, or neoplasia
- endothelial damage
- proteolytic enzymes present in snake venoms and trypsin released during pancreatitis
- stagnant blood flow
- inflammation
- heat stroke
What are the 2 phases to disseminated intravascular coagulation (DIC)?
- hypercoagulable phase - thrombosis leading to ischemic necrosis and organ dysfunction
- consumptive phase - cosumption of platelets, coagulation factors, and antithrombin leading to bleeding and increased fibrinolysis
What is the pathogenesis of disseminated intravascular coagulation (DIC)?
- some primary disease process activates coagulation
- hypercoagulable phase induces the formation of thrombi (fibrin clots) that can block microvasculature and induce ischemic necrosis, causing ORGAN DYSFUNCTION
- thrombus formation also induces fibrinolysis and consumptive phase
- FDPs increase at a rate higher than macrophages are able to consume them, decreasing platelet function and inhibition of fibrin polymerization
- platelets and coagulation factors are simultaneously decreased, all causing BLEEDING
What are the 3 common clinical signs of disseminated intravascular coagulation?
- associated signs of primary disease
- signs of organ dysfunction secondary to thrombosis
- mucosal bleeding due to platelet consumption and hemorrhage due to factor comsumption
What are 6 common laboratory findings in patients with disseminated intravascular coagulopathy (DIC)? What is commonly seen on a blood smear? What must be present for an accurate diagnosis?
- thrombocytopenia (mild to moderate)
- prolonged PT, aPTT, and ACT
- decreased fibrinogen concentration
- decreased antithrombin (AT)
- increased FDPs and D-dimers
- hemorrhagic anemia
RBC morphology indicative of fragmental injury: schistocytes, keratocytes, acanthocytes
3/4 of these must be seen on bloodwork
How can liver disease cause coagulopathies?
- decreased synthesis of coagulation factors
- production of dysfunctional factors due to a failure in metabolizing/reducing vitamin K
(coagulopathies must be screened for prior to liver biopsies)
What are the 3 major coagulation factors that can be decreased due to inherited deficiencies? When should thses diseases be a part of differential diagnoses?
8 (hemophilia A), 9 (hemophilia B), 12 (cats)
young animals with bleeding disorders
CASE: A 5 y/o FS indoor/outdoor DSH cat is reported to be “not herself” over the last 2 days. There is suspected access to rodenticide recently put out in the apartment building. No blood is observed in the urine or feces. Physical exam shows that the cat is quiet, but bright, alert, and responsive.
Which pathway(s) of the coagulation cascade are we testing with an aPTT test? What factors are examined in this test? Why do these results rule out rodenticide toxicity? What are some Ddx?
- intrinsic and common pathways
- 12, 11, 9, 8; 2 (prothrombin), 5, 10, 1 (fibrinogen) - DOES NOT test for 7 (tissue factor) or 13 (fibrin)
- absence of prolongation in PT rules out rodenticide toxicity - Factor VII has the shortest half-life, so the extrinsic pathway (tested by PT) will be the first to show prolonged clotting time
Ddx:
- Hageman’s disease (Factor XII deficiency): condition shows no clinical signs of bleeding, but may result in aPTT prolongation
- hemophilia: rare in cats and unlikely in a cat of this age without previous clinical signs of bleeding
CASE: A 9 y/o F Dachshund dog has been coughing and shown hematuria for 1 week without response to broad-spectrum antibiotics and mucolytic treatment. Weight loss of 2.5 kg was noted within the last 4 months. Physical exam shows several hematomas observed at injection sites along with 3 firm mammary tumors palpated at the mammary complex of the right side. Thoracic radiographs revealed an interstitial lung pattern and a clearly visible pleural fissure indicative of slight thoracic effusion. Moderate hepatosplenomegaly was detected. A calcified mass was observed causal to the costal arch consistent with a subcutaneous tumor.
Describe and discuss the significant hematological and coagulation findings. What is the most likely etiology of the abnormalities? What prognosis is associated with the diagnosis?
HEMATOLOGY:
- slight regenerative anemia likely due to subacute hemorrhage give Hx and Px
- slight mature (no bands) neutrophilia and monocytosis suggesting corticosteroid stress leukogram
- moderate thrombocytopenia most likely due to consumption or loss (blood film shows large/giant platelets, indicating regeneration so it is not due to decreased production)
COAGULATION PROFILE:
- prolonged PT and aPTT shows that intrinsic, extrinsic, and common pathways are affected
- severe hypofibrinogenemia
- marked increase in D-dimers indicative of increasd coagulation activity and fibrinolysis
- moderate decrease in antithrombin
DIC —> Given PE findings, the mammary tumors are the most probable etiology. Metastasis to the lungs give the seen abnormalities. Prognosis is poor as these cases are not responsive to treatment unless the tumor is removed. Unfortunately, surgery cannot be recommended given the poor coagulation status
Disorders and diagnostic tests:
