Hematology , Toxicology

Coagulopathies in Veterinary Patients: When Is It Rat Poison?

Coagulopathies in Veterinary Patients: When Is It Rat Poison?


Debra Liu, DVM, Diplomate ACVECC, and Lesley G. King, MVB, Diplomate ACVECC & ACVIM (Small Animal Internal Medicine)

In 2015, d-CON will comply with EPA mandates regarding anticoagulant rodenticides for household use. Learn the ins and outs of coagulopathies through a case study presented by Dr. Liu including diagnostics, primary and secondary hemostatic defects, and treatment.

A 3-year-old, 20-kg neutered male mixed breed dog was presented for acute hemoptysis.


A few hours prior to presentation, the owner noticed that the dog was weak and coughing up blood. No vomiting, diarrhea, or changes in urination were reported. He was the only pet, and kept in a fenced yard. The dog was current on vaccinations, and not receiving any medications.


The mucous membranes were pale pink, with a capillary refill time of 1.5 seconds. Some blood was noted in the oral cavity. Heart sounds were normal, with a rate of 140 beats per minute; pulses were strong. He was mildly tachypneic, with harsh lung sounds auscultated bilaterally.During the examination, the dog started coughing. The cough sounded wet, and more blood was expectorated. No petechiae or ecchymoses were found. Normal stool was seen on rectal examination. The rest of the physical examination was within normal limits (WNL).


Based on history and physical examination, trauma was not considered a likely diagnosis. The main differentials considered were:

  • Coagulopathy
  • Bleeding primary lung lesion, such as a neoplasm.


Laboratory Analysis

Blood smear examination revealed an adequate number of platelets (estimated 250,000/mcL); morphology and number of white and red blood cells were WNL. Packed cell volume was 30%, and total solids were 6 g/dL.

Other Diagnostics

Pulse oximetry measured hemoglobin oxygen saturation at 96% on room air. Chest radiographs demonstrated an asymmetrical, patchy alveolar lung pattern and small amount of pleural effusion (Figure).

Figure. Chest radiographs of a 3-year-old neutered male mixed breed dog presented with hemoptysis; note the patchy alveolar lung pattern (blue arrow) and small amount of pleural effusion (red arrow) present.

Figure 1 a

Figure 1 b


Because the radiographs did not document a specific lung lesion, such as a neoplastic mass, additional testing was warranted. Pertinent results from additional blood analysis are listed in Table 1.

Complete blood count and serum biochemical profile were WNL, except for mild anemia. Prothrombin time (PT) was extremely prolonged, and activated partial thromboplastin time (aPTT) was mildly prolonged.

Table 1. Additional Blood Analysis: Pertinent Results
Hematocrit (%)
Prothrombin time (sec)
> 200
Activated partial thromboplastin time (sec) 18 10.7—16.4


Based on the clinical signs and diagnostic findings in this dog, a secondary coagulopathy (ie, defect of coagulation factors) was suspected (Table 2). See General Approach to Coagulopathies for further information on primary and secondary coagulopathies.

Table 2. Differentials for Common Secondary Hemostatic Defects
Dilutional coagulopathy due to fluid therapy
Normal or down
Disseminated intravascular coagulopathy
Up or normal
Up or normal
Normal or down
Normal or down
Heparin overdose
Hepatic dysfunction
Up or normal
Up or normal
Hereditary deficiency of clotting factor VIII, IX, XI, or XII
Up Normal
Hereditary deficiency of clotting factor VII
Hereditary deficiency of clotting factor II, X, or fibrinogen
Up Normal
Vitamin K deficiency (Table 3) Up Up or normal Normal Normal or down

Measurement of D-dimers

In addition to measuring PT, aPTT, and platelet count, measuring d-dimers and fibrin degradation products (FDPs) may be helpful in distinguishing between different types of secondary defects.

D-dimers are a type of FDP derived specifically from breakdown of cross-linked fibrin. Increased blood levels of d-dimers and/or FDPs detect activation of the fibrinolytic system, which is activated whenever coagulation factors are consumed. This activation is common in animals with intravascular thrombosis and/or disseminated intravascular coagulopathy.

FDPs and D-dimers are removed from circulation by the liver; therefore, they also may be mildly to moderately elevated in animals with liver disease.

Definitive Diagnosis

In this dog, the D-dimer concentration was 0.15 mcg/mL (reference range, < 0.2 mcg/mL). This normal result, combined with a severely prolonged PT, mildly prolonged aPTT, and normal platelets strongly suggested a clinical diagnosis of anticoagulant rodenticide toxicity (vitamin K deficiency); however, hereditary clotting factor VII deficiency could not be ruled out completely.

Diagnosis of anticoagulant rodenticide toxicity is often clinically confirmed retrospectively based on a favorable response to vitamin K1 therapy. If PT remains persistently prolonged despite vitamin K1 supplementation, clotting factor analysis is necessary to diagnose hereditary deficiency of clotting factor VII.

Pathophysiology of Anticoagulant Rodenticide Toxicosis

Anticoagulant rodenticides block the recycling of vitamin K epoxide to vitamin K hydroquinone, which is an essential cofactor in hepatic synthesis of functional clotting factors II, VII, IX, and X. The half-lives of these clotting factors are 40, 6, 14, and 16 hours, respectively. Depletion of these clotting factors affects the extrinsic, intrinsic, and common coagulation pathways, resulting in clinical bleeding typically 2 to 5 days post exposure.

Anticoagulant Rodenticide Toxicity

In anticoagulant rodenticide toxicity:

  1. PT becomes prolonged first (usually 48—72 hours post toxin ingestion) due to the short half-life of clotting factor VII (4—6 hours).
  2. As other functional vitamin K-dependent clotting factors deplete with time, aPTT and activated clotting time (ACT) then become prolonged as well. Therefore, with anticoagulant rodenticide toxicity, PT is disproportionally prolonged compared to aPTT.
  3. Platelets are not directly affected by anticoagulant rodenticides, although in animals with severe bleeding, platelet counts may drop significantly as platelets are consumed in an attempt to stop hemorrhaging.

General Approach to Coagulopathies

Coagulopathies are divided into defects of primary or secondary hemostasis (Table 3):

  • Defects of primary hemostasis occur when the number or function of platelets is abnormal, or when an abnormality of the blood vessel endothelium, such as vasculitis, exists
  • Defects of secondary hemostasis involve insufficient or ineffective coagulation factors
Table 3. Common Causes of Primary & Secondary Hemostatic Defects
Causes of deficient number of platelets:
  • Accelerated platelet consumption (hemorrhage, thrombosis, disseminated intravascular coagulopathy)
  • Bone marrow suppression (neoplasia, myelofibrosis, toxins)
  • Primary or secondary immune-mediated thrombocytopenia (idiopathic, drug-induced, neoplasia-induced, tick-borne or other infectious diseases)
  • Splenic sequestration (splenic torsion, infarction, neoplasia)

Causes for abnormal function of platelets:

  • Hereditary or acquired platelet dysfunction (von Willebrand’s disease, uremia, intrinsic platelet disorders)
  • Dilutional coagulopathy due to fluid therapy
  • Disseminated intravascular coagulopathy
  • Envenomation
  • Heparin overdose
  • Hepatic dysfunction
  • Hereditary clotting factor deficiency
  • Vitamin K deficiency:
    • Anticoagulant rodenticide toxicosis
    • Cholestasis
    • Intestinal malabsorption
    • Intestinal sterilization from prolonged antibiotic use
    • Malnutrition

While there is no absolute rule regarding location of bleeding:

  • Primary hemostatic defects tend to cause surface bleeding, such as petechiae of the oral mucosa, gastrointestinal tract (melena or hematemesis), thin skinned areas of the body, or epistaxis
  • Secondary hemostatic defects commonly result in cavitary bleeding.

Clinical presentation often helps prioritize the initial list of differentials, recognizing that the 2 categories of bleeding disorders overlap (Table 4), and definitive diagnosis requires further diagnostic testing.

Table 4. Primary Versus Secondary Hemostatic Defects: Common Locations of Bleeding
Surface bleeding, such as hemorrhage, petechiae, or ecchymoses of skin and mucous membranes:
  • Gastrointestinal tract
  • Genitourinary tracts
  • Nasal mucosa
  • Ocular: conjunctiva, sclera, iris, retina
  • Oral mucosa
  • Respiratory tract, including pulmonary parenchyma
  • Thin skinned areas: Ventral thorax and abdomen, especially at axillary and inguinal areas; pinnae and medial aspects of limbs are also commonly affected
Cavitary bleeding:
  • Between fascial planes of the muscles
  • Cranium: Subdural space and ventricles
  • Joint space
  • Mediastinum
  • Pericardial space
  • Peritoneal space
  • Pleural space
  • Respiratory tract, including pulmonary parenchyma




The dog was treated with 2 units of fresh frozen plasma, and vitamin K1 therapy was initiated (2.5 mg/kg PO Q 12 H). Recheck PT and aPTT were WNL after the transfusion. The patient remained stable, with no further evidence of bleeding, and was discharged the next day with a course of vitamin K1 therapy. The owner reported that coughing subsided in 3 to 4 days.

Vitamin K1 Therapy

Vitamin K1 is the most commonly used antidote for anticoagulant rodenticide. It is a more effective and safer therapeutic agent than vitamin K3, which has been reported to cause hemolytic anemia in dogs.

Administration. Vitamin K1 is well absorbed orally and subcutaneously. Gastrointestinal absorption can be further enhanced by feeding a fatty meal at time of drug administration, and portal circulation carries the absorbed vitamin K1 to the liver directly for clotting factor production.

Anaphylaxis has been reported with intravenous vitamin K1 administration; intramuscular injections may cause local hemorrhage and should be avoided in hypocoagulable animals.

Duration. The necessary duration of vitamin K1 therapy is directly related to the elimination half-life of the anticoagulant rodenticide ingested.

  • First-generation anticoagulant rodenticides (eg, warfarin, coumarin) are metabolized within 14 days.
  • Second-generation anticoagulant rodenticides (eg, bromadiolone, brodifacoum) are more potent, with prolonged toxic effects, requiring 4 weeks of therapy or, in some cases, longer.

At-Home Therapy

In this case, since the exact type of anticoagulant rodenticide ingested was unknown, a 4-week course of therapy was prescribed. A follow-up appointment was planned to re-evaluate PT 48 to 72 hours after completion of treatment to ensure adequate duration of therapy.


Four weeks later, the dog was presented for recheck PT testing 48 hours after the last dose of vitamin K1. PT was normal, and the dog made a full recovery.

If residual toxin had remained, PT would have become prolonged during the 48 to 72 hours after therapy completion. In these cases, vitamin K1 supplementation should be administered for another 1 to 2 weeks, and PT re-evaluated at therapy end.


To avoid repeat ingestion, it is important to ask owner to:

  • Thoroughly inspect the home environment and remove any remaining rodenticide found on premises
  • Search for, and remove, rodenticide from any place that the pet may have visited during the past few days, as bleeding due to anticoagulant rodenticide typically begins 2 to 5 days after exposure.

Repeat ingestion of similar toxins may cause relapse of bleeding once vitamin K1 therapy is discontinued.

The Changing Face of Rodenticides

Most veterinarians are familiar with traditional anticoagulant-type rodenticides, including:

  • First-generation anticoagulant rodenticides (ie, warfarin, chlorophacinone, diphacinone)
  • Second-generation anticoagulant rodenticides (ie, brodifacoum, bromadiolone).

All of these products have the same mechanism of action, and clinical management is similar, apart from duration of treatment with vitamin K1.

However, in 2011, in an effort to reduce relay or secondary poisoning in wildlife, the Environmental Protection Agency (EPA) banned the use of second-generation anticoagulant rodenticides for household use. Manufacturers were left with the choice of using first-generation anticoagulants, bromethalin, or cholecalciferol (vitamin D3).

The latter 2 rodenticides are highly toxic and act through different mechanisms than anticoagulant-type rodenticides. Accidental poisonings in pets are difficult to manage.

Reckitt Benckiser (rb.com), the manufacturer of d-CON, the largest selling rodenticide in the U.S., fought the EPA mandate, stating that the ban would lead to increased bromethalin use, increasing the risk of poisoning in pets and children due to its potency as a neurotoxin and the lack of an antidote.

Sales of d-CON products containing the second-generation anticoagulant rodenticide brodifacoum were allowed to continue during Reckitt Benckiser’s ongoing legal battle with the EPA. Meanwhile, bromethalin became the active ingredient of choice by compliant rodenticide manufacturers and bromethalin poisoning cases reported to the Pet Poison Helpline (petpoisonhelpline.com) increased by 65%.

In May 2014, d-CON announced that it would comply with EPA mandates, but would be using the first-generation anticoagulant rodenticide diphacinone, which has a longer duration of action than warfarin. The new product line will be introduced in 2015.


Anticoagulant rodenticides are a common cause of coagulopathy encountered in veterinary medicine.

  • Clinical presentation of this bleeding diathesis is variable and shared by many other hemostatic disorders.
  • Acute hemoptysis alone is a less common clinical presenting complaint.
  • Initial clinical signs are often vague and may include lethargy, weakness, or acute dyspnea due to cavitary bleeding in the chest and/or abdomen.
  • A systematic approach to differentiate anticoagulant rodenticide toxicity from other hemostatic disorders is key to early diagnosis and successful treatment.

ACT = activated clotting time; aPTT = activated partial thromboplastin time; EPA = environmental protection agency; FDPs = fibrin degradation products; PT = prothrombin time; WNL = within normal limits

Suggested Reading

Brooks MB, De Laforcade A. Acquired coagulopathies. In Weiss DJ, Wardrop KJ (eds): Schalm’s Veterinary Hematology, 6th ed. Ames, IA: Blackwell Publishing, 2010, pp 654-660.

Brooks MB. Hereditary coagulopathies. In Weiss DJ, Wardrop KJ (eds): Schalm’s Veterinary Hematology, 6th ed. Ames, IA: Blackwell Publishing, 2010, pp 661-667.

Brown AJ, Waddell LS. Rodenticides. In Silverstein DC, Hopper K (eds): Small Animal Critical Care Medicine. St. Louis: Saunders Elsevier, 2009, pp 346-348.

Felice LJ, Murphy MJ. CVT update: Anticoagulant rodenticides. In Bonagura JD (ed): Kirk’s Current Veterinary Therapy XII: Small Animal Practice. Philadelphia: WB Saunders Company, 1995, pp 228-232.

Fernandez FR, Davies AP, Teachout DJ, et al. Vitamin K-induced Heinz body formation in dogs. JAAHA 1984; 20:711-720.

Mount ME, Woody BJ, Murphy MJ. The anticoagulant rodenticides. In Kirk RW (ed): Current Veterinary Therapy IX: Small Animal Practice, 9th ed. Philadelphia: WB Saunders, 1986, pp 156-165.

Murphy MJ, Gerken DF. The anticoagulant rodenticides. In Kirk RW (ed): Current Veterinary Therapy X: Small Animal Practice, 10th ed. Philadelphia: WB Saunders, 1989, pp 143-146.

Scott MA, Jutkowitz LA. Immune-mediated thrombocytopenia. In Weiss DJ, Wardrop KJ (eds): Schalm’s Veterinary Hematology, 6th ed. Ames, IA: Blackwell Publishing, 2010, pp 586-595.

F02_bDebra Liu, DVM, Diplomate ACVECC, is medical director of the Veterinary Emergency Service in Fresno and staff criticalist at VCA Orange County Veterinary Specialists in Tustin, California. She received her DVM from Iowa State University and completed a small animal medicine and surgery internship at University of Minnesota. She completed a residency in small animal emergency and critical care at University of Pennsylvania.

F02_cLesley G. King, MVB, Diplomate ACVIM & ACVECC, is professor of critical care and director of the intensive care unit at University of Pennsylvania School of Veterinary Medicine. She is also editor in chief of Today’s Veterinary Practice. She graduated from Faculty of Veterinary Medicine, University College Dublin, Ireland, and completed a small animal internal medicine residency at University of Pennsylvania.

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Guiana</option><option value='French Polynesia' >French Polynesia</option><option value='French Southern Territories' >French Southern Territories</option><option value='Gabon' >Gabon</option><option value='Gambia' >Gambia</option><option value='Georgia' >Georgia</option><option value='Germany' >Germany</option><option value='Ghana' >Ghana</option><option value='Gibraltar' >Gibraltar</option><option value='Greece' >Greece</option><option value='Greenland' >Greenland</option><option value='Grenada' >Grenada</option><option value='Guadeloupe' >Guadeloupe</option><option value='Guam' >Guam</option><option value='Guatemala' >Guatemala</option><option value='Guernsey' >Guernsey</option><option value='Guinea' >Guinea</option><option value='Guinea-Bissau' >Guinea-Bissau</option><option value='Guyana' >Guyana</option><option value='Haiti' >Haiti</option><option value='Heard and McDonald Islands' >Heard and McDonald Islands</option><option value='Holy See' >Holy See</option><option value='Honduras' >Honduras</option><option value='Hong Kong' >Hong Kong</option><option value='Hungary' >Hungary</option><option value='Iceland' >Iceland</option><option value='India' >India</option><option value='Indonesia' >Indonesia</option><option value='Iran' >Iran</option><option value='Iraq' >Iraq</option><option value='Ireland' >Ireland</option><option value='Isle of Man' >Isle of Man</option><option value='Israel' >Israel</option><option value='Italy' >Italy</option><option value='Jamaica' >Jamaica</option><option value='Japan' >Japan</option><option value='Jersey' >Jersey</option><option value='Jordan' >Jordan</option><option value='Kazakhstan' >Kazakhstan</option><option value='Kenya' >Kenya</option><option value='Kiribati' >Kiribati</option><option value='Kuwait' >Kuwait</option><option value='Kyrgyzstan' >Kyrgyzstan</option><option value='Lao People&#039;s Democratic Republic' >Lao People&#039;s Democratic Republic</option><option value='Latvia' >Latvia</option><option value='Lebanon' >Lebanon</option><option value='Lesotho' >Lesotho</option><option value='Liberia' >Liberia</option><option value='Libya' >Libya</option><option value='Liechtenstein' >Liechtenstein</option><option value='Lithuania' >Lithuania</option><option value='Luxembourg' >Luxembourg</option><option value='Macau' >Macau</option><option value='Macedonia' >Macedonia</option><option value='Madagascar' >Madagascar</option><option value='Malawi' >Malawi</option><option value='Malaysia' >Malaysia</option><option value='Maldives' >Maldives</option><option value='Mali' >Mali</option><option value='Malta' >Malta</option><option value='Marshall Islands' >Marshall Islands</option><option value='Martinique' >Martinique</option><option value='Mauritania' >Mauritania</option><option value='Mauritius' >Mauritius</option><option value='Mayotte' >Mayotte</option><option value='Mexico' >Mexico</option><option value='Micronesia' >Micronesia</option><option value='Moldova' >Moldova</option><option value='Monaco' >Monaco</option><option value='Mongolia' >Mongolia</option><option value='Montenegro' >Montenegro</option><option value='Montserrat' >Montserrat</option><option value='Morocco' >Morocco</option><option value='Mozambique' >Mozambique</option><option value='Myanmar' >Myanmar</option><option value='Namibia' >Namibia</option><option value='Nauru' >Nauru</option><option value='Nepal' >Nepal</option><option value='Netherlands' >Netherlands</option><option value='New Caledonia' >New Caledonia</option><option value='New Zealand' >New Zealand</option><option value='Nicaragua' >Nicaragua</option><option value='Niger' >Niger</option><option value='Nigeria' >Nigeria</option><option value='Niue' >Niue</option><option value='Norfolk Island' >Norfolk Island</option><option value='North Korea' >North Korea</option><option value='Northern Mariana Islands' >Northern Mariana Islands</option><option value='Norway' >Norway</option><option value='Oman' >Oman</option><option value='Pakistan' >Pakistan</option><option value='Palau' >Palau</option><option value='Palestine, State of' >Palestine, State of</option><option value='Panama' >Panama</option><option value='Papua New Guinea' >Papua New Guinea</option><option value='Paraguay' >Paraguay</option><option value='Peru' >Peru</option><option value='Philippines' >Philippines</option><option value='Pitcairn' >Pitcairn</option><option value='Poland' >Poland</option><option value='Portugal' >Portugal</option><option value='Puerto Rico' >Puerto Rico</option><option value='Qatar' >Qatar</option><option value='Réunion' >Réunion</option><option value='Romania' >Romania</option><option value='Russia' >Russia</option><option value='Rwanda' >Rwanda</option><option value='Saint Barthélemy' >Saint Barthélemy</option><option value='Saint Helena' >Saint Helena</option><option value='Saint Kitts and Nevis' >Saint Kitts and Nevis</option><option value='Saint Lucia' >Saint Lucia</option><option value='Saint Martin' >Saint Martin</option><option value='Saint Pierre and Miquelon' >Saint Pierre and Miquelon</option><option value='Saint Vincent and the Grenadines' >Saint Vincent and the Grenadines</option><option value='Samoa' >Samoa</option><option value='San Marino' >San Marino</option><option value='Sao Tome and Principe' >Sao Tome and Principe</option><option value='Saudi Arabia' >Saudi Arabia</option><option value='Senegal' >Senegal</option><option value='Serbia' >Serbia</option><option value='Seychelles' >Seychelles</option><option value='Sierra Leone' >Sierra Leone</option><option value='Singapore' >Singapore</option><option value='Sint Maarten' >Sint Maarten</option><option value='Slovakia' >Slovakia</option><option value='Slovenia' >Slovenia</option><option value='Solomon Islands' >Solomon Islands</option><option value='Somalia' >Somalia</option><option value='South Africa' >South Africa</option><option value='South Georgia' >South Georgia</option><option value='South Korea' >South Korea</option><option value='South Sudan' >South Sudan</option><option value='Spain' >Spain</option><option value='Sri Lanka' >Sri Lanka</option><option value='Sudan' >Sudan</option><option value='Suriname' >Suriname</option><option value='Svalbard and Jan Mayen Islands' >Svalbard and Jan Mayen Islands</option><option value='Sweden' >Sweden</option><option value='Switzerland' >Switzerland</option><option value='Syria' >Syria</option><option value='Taiwan' >Taiwan</option><option value='Tajikistan' >Tajikistan</option><option value='Tanzania' >Tanzania</option><option value='Thailand' >Thailand</option><option value='Timor-Leste' >Timor-Leste</option><option value='Togo' >Togo</option><option value='Tokelau' >Tokelau</option><option value='Tonga' >Tonga</option><option value='Trinidad and Tobago' >Trinidad and Tobago</option><option value='Tunisia' >Tunisia</option><option value='Turkey' >Turkey</option><option value='Turkmenistan' >Turkmenistan</option><option value='Turks and Caicos 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