Disseminated Intravascular Coagulation: A Case-Based Approach

Oncology Nursing Society 43nd Annual CongressMay 17–20, 2018 • Washington, DC 1Clinical Practice

Rebecca Martin, BSN, RN, OCN, BMTCNStaff RN/Educator Froedtert Hospital [email protected]

Key Session Takeaways1. Attendees will be able to identify the early signs and symptoms of

oncology-related disseminated intravascular coagulation (DIC).2. Attendees will learn about treatment options for oncology-related

DIC.3. Attendees will be able to develop a nursing plan of care for the

patient with oncology-related DIC.

Disseminated Intravascular Coagulation: A Case-Based ApproachThursday, May 17 • 9:45–11 am

Note one action you’ll take after attending this session: ____________________________________________________

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ONS 43rd Annual Congress

Clinical Practice 1

Disseminated Intravascular Coagulation: A Case-Based ApproachRebecca Martin BSN RN OCN BMTCN

Staff RN/Educator Froedtert Hospital/Medical College of Wisconsin

Disclosures

• I have no disclosures


Clinical Practice 2

Objectives• List risk factors of DIC in oncology patients• Recognize signs and symptoms of DIC in

oncology patients• Discuss treatment strategies of DIC in oncology

patients

DIC• An acquired syndrome characterized by the the

simultaneous presence of thrombin and plasmin• It can originate from and cause damage to the

microvasculature – If sufficiently severe, can produce organ dysfunction

-subcommittee on DIC of the International Society on Thrombosis and Haemostasis

• Over activation of clotting cascade and fibrinolysisThachil, et. al. 2014

Pathophysiology• Monocytes and endothelial cells are activated or

injured• Their response is to generate tissue factor on

the cell surface, activating the coagulation cascade


Clinical Practice 3

Toh, 2013

DIC• Always occurs secondary to an underlying

disorder• Must recognize and treat the underlying

disorder so that effective therapy can be instituted

DIC• DIC may occur in 30-50% of patients with

sepsis• Difficult to estimate frequency in oncology

patients –frequently diagnosed on autopsy• A high mortality rate associated with DIC,

however typically due to the underlying disease


Clinical Practice 4

Cancer Related DIC• First described by Trousseau in 1865• Most common malignancies

– APL– Adenocarcinoma– Breast, lung, prostate, colorectal

• Most commonly in stage III-IV• Increased incidence with liver mets and increased age

APL and DIC• Most present with a coagulopathy• Overproduction of plasmin and fibrinolysis• Initiate all-trans-retinoic-acid immediately

– Will control DIC• Keep platelets >20K• Keep fibrinogen >100mg/dL

Liver Disease and DIC• Can decrease the production and function of

platelets and fibrinogen• Plays a significant role in treatment plan due to

potential prognosis implications


Clinical Practice 5

Solid Tumors and DIC• Large prospective study in DIC and solid

tumors (n=1117) –Sallen, et.al. (2001)• Significant independent factors

– Age, male, higher staged cancer, breast cancer, presence of necrosis in tumor specimen

• Management variedFeinstein, 2015

Solid Tumors and DIC• Patients with advanced disease and DIC

– Median survival 9 months vs. 14 months without DIC

• Patients with stage I/II disease and DIC– Median survival 16 months vs. 44 months without DIC

Sallen, et.al. (2001)

Solid Tumors and DIC• Typically chronic and slow moving

– May lead to a normalized fibrinogen due to liver compensatory strategies

• Difficult to diagnose– Serial lab observation– Treatment of underlying disorder


Clinical Practice 6

Solid Tumors and DIC• Mechanism of action

– Generation of tissue factor by tumor cells• Increased tissue factor binds to factor VII, activating

factors IX and X

– Tissue factor is expressed by endothelial cells– Endothelial cells regulate coagulation

Cancer Related DIC• Procoagulant• Hyperfibrinolytic• Subclinical

Procoagulant DIC• Increased thrombin leading to thrombosis• Adenocarcinoma and pancreatic• Symptoms

– Related to intravascular thrombosis• Treatment

– Treat underlying disorder– Consider anticoagulation


Clinical Practice 7

Hyperfibrinolytic DIC• Increased fibrinolysis• APL and metastatic prostate• Symptoms

– Bleeding• Treatment

– Treat underlying cause– Support

Subclinical DIC• Lab changes without bleeding or clotting• Many solid cancers• Symptoms

– None• Treatment

– Treat underlying cause– Monitor/trend labs– Consider prophylactic anticoagulation

Laboratory Findings

Platelet Decreased

PT/PTT/INR Prolonged

Fibrinogen Decreased

FDP Increased

D‐Dimer Increased

RBC Morphology Presence of Schistocytes


Clinical Practice 8

Platelet Count• An increased platelet count is a negative

prognostic indicator in patients with DIC• Short life span –especially in DIC

PT/PTT/INR• May not be prolonged in cancer-related DIC

– Initial activation of the coagulation system by a malignancy can even shorten the PTT

– Potential for mild decrease in Subclinical DIC

• Abnormal in only 50% of sepsis-related DIC

PT/PTT/INR• Other causes of impairment in cancer patients

– Liver impairment– Vitamin K deficiency– Dysfibrinogenemia– Paraproteinemias– Acquired inhibitors of coagulation factors


Clinical Practice 9

Fibrinogen• Soluble protein• Broken down by thrombin to form clots• Procoaculant DIC

– Rarely decreased • Hyperfibrinolytic DIC

– Extreme and rapid decrease

D-Dimer• Protein present in the blood after a blood clot is

degraded by fibrinolysis – Present once the coagulation system has been

activated

• Normal value <0.5• Trend value in patients at risk for DIC

D-Dimer

• False positives– Liver disease– Inflammation– Malignancy– Ascitis– Pleural effusion– Soft tissue picture

– Trauma– Pregnancy – Recent surgery – Advanced age– Insufficiently filled tube


Clinical Practice 10

D-Dimer• Hyperfibrinolytic DIC

– Very high– Can be decreased with appropriate therapy

• Procoagulant and Subclinical DIC– Varying leveles

The International Society of Thrombosis and Hemostasis DIC Score

Platelet Count >100K 0 points

<100K 1 point

<50K 2 points

Fibrinogen >100 mg/dL 0 points

<100 mg/dL 1 point

Prothrombin Time Prolonged < 3 seconds 0 points

Prolonged 3‐5 seconds 1 point

Prolonged ≥6 seconds 2 points

D‐Dimer or FDP No increase 0 points

Moderate increase 2 points

Strong increase 3 points

Clinical Manifestations• Bleeding• Renal dysfunction• Hepatic dysfunction• Respiratory dysfunction• CNS involvement• Other systemic signs/symptoms –due to

underlying pathophysiology



Nursing Assessment• Frequent physical assessments

– Watch for and report subtle changes• Trend lab values• Monitor vital signs every 1-2 hours• Monitor I & O to avoid complications of

dehydration

Nursing AssessmentNeuro

HEENT

Genitourinary

Gastrointestinal

Cardiovascular

Respiratory

Musculoskeletal

Skin

Pain

Treatment • Early recognition• Treat the underlying problem• Supportive care• Inhibition of excess thrombin

Per the ISTH-SCC (International Society on Thrombosis and Haemostasis, Scientific and Standardization Committee)



Supportive Care• DIC and active bleeding

– Keep platelets >50K– Keep fibrinogen >100 mg/dl

• High risk for DIC– APL –keep platelets >30K– Other –keep platelets >20K

Supportive Care• What if volume is an issue?

– Consider use of Prothrombin Complex Concentrates• Factor IX –Beriplex, Octaplex, Kcentra• Black box warning –could stimulate DIC by activating the

clotting cascade

Supportive Care• Cryoprecipitate

– Given if fibrinogen <100 mg/l– Centrifuge FFP and collect the precipitate

• Factor VIII

– ABO compatible whenever possible



Inhibition of Excess Thrombin• Prothrombotic DIC

– Prophylactic anticoagulation• Monitor platelet count and signs and symptoms of bleeding

• Subclinical DIC– Anticoagulation has shown benefit

• Hyperfibrinolytic– Avoid anticoagulation

Anticoagulation• Not contraindicated due to abnormal coags,

without bleeding• Heparin –frequently preferred over LMWH

– Especially if high risk of bleeding or renal failure– Easier to reverse– Monitor anti-Fxa activity (UFH level) not PTT

Antifibrinolytic Agents• Tranexamic Acid (Lysteda) or Animocaproic Acid

(Amicar)– Not shown to be effective in APL– May be useful in therapy-resistant bleeding in

Hyperfibrinolytic DIC– Increase risk of DVT

• Recombinant Factor VIIa– Uncertain efficacy– Definite increase in thrombotic events



IVC Filter• Use only if evidence of LE DVT and

anticoagulation is not an option• Could activate the coagulation system

Case StudyJB

27 year old female

Past Medical History• Large T-cell lymphoma

– Diagnosed November

• Upon Diagnosis– DVT right upper extremity– Left lower lobe PE



Presenting signs and symptoms• Typical

– Painless swelling in the neck, arm pit or groin, loss of appetite or tiredness

– B symptoms• JB’s presenting signs and symptoms

– Right axillary and supraclavicular lymphadenopathy• Swelling of the right arm, breast and neck

Diagnosis• Typical

– Lymph node biopsy– Blood tests, x-rays, scans, bone marrow biopsy

• JB– MRI– Right supraclavicular node biopsy– Negative bone marrow biopsy

Diagnosis• At time of diagnosis JB had compression of the

right subclavian and axillary veins as well as DVT of right upper extremity

• 14 weeks pregnant– Therapeutic pregnancy termination



Treatment Timeline

Martin, 2017

Transplant• Transplant statistics:

– No transplant-15% long term survival– Transplant- 40-50% long term survival

2% TRM• Conditioned with BEAM: carmustine, etoposide, ara-c,

melphalan• Auto transplant December • Transplant course unremarkable-discharged on Day +12

with good engraftment

Post-Transplant Readmission• February

– Admitted after 48 hours of nausea, vomiting, diarrhea, fever, cough and rhinorrhea at home



Hospitalization Issues• Pancytopenia• Influenza• Diarrhea• Menorrhagia• Back pain• Skin rash

Readmission Week One

February5

Admit with URI symptoms, fever and diarrhea

6 7 8 9Afebrile, decreased diarrhea

10Febrile and increased diarrhea

11CT –new sites of ground glass infiltrates

Vanco and Cipro started

Vanco and Cipro dc’d

Vanco and Cipro restarted

Repeat BAL

Vanco dc’d

Readmission Week Two

February12 13

Diarrhea and rash

14 15Coagulopathy noted

16Colonoscopy

17 18

SteroidsFFP and

Vitamin K



Readmission Week ThreeFebruary

19All biopsies negative

20Fevers Cultures NGTDSpleen and Kidney Infarcts

21Evidence of DICFluid overloadNegative Echo

22 23DIC continuesLarge right MCADecreased LOC

24Decreased LOCIncreased oxygen needsDIC Continues

25Herniation and minimal brain activity

Steroid taper

Vanco restarted

Lasix

Supportive Care –Blood

Products

Heparin drip

IntubationMannitol

HyperventilationHeparin drip

increased

Comfort Measures

Kidney Infarct

Used with permission from Froedtert Hospital

Splenic Infarct



Key Takeaways• Identification of early signs and symptoms of

oncology-related DIC• Treatment options of oncology-related DIC• Development of a nursing plan of care for the

patient with oncology-related DIC

References• Thachil J, Falanga A, Levi M, Liebman H, Di Nisio M. Management of cancer-associated disseminated

intravascular coagulation: guidance from the SCC of the ISTH. J Thromb Haemost 2015; 13:671-5• Feinstein, D. Disseminated intravascular coagulation in patients with solid tumors. Oncology-Journal 2015; 2.• Sallah S, Wan JY, Hguyen NP, et al. Disseminated intravascular coagulation in solid tumors: clinical and

pathologic study. J Thromb Haemost. 2001; 86:828-33• Anselmo M, Nobre de Jesus G, Lopes, J et al. Massive bleeding as the first clinical manifestation of

metastatic prostate cancer due to disseminated intravascular coagulation with enhanced fibrinolysis. Case Reports in Hematology 2016.

• Toh CH, Alhamdi Y. Current consideration and management of disseminated intravascular coagulation. American Society of Hematology. 2013; 1:286-91

Documents

Disseminated Intravascular Coagulation: A Case-Based Approach