Malignant Melanoma <-> Disseminated Intravascular Coagulation

name: com_Malignant_Melanoma__Disseminated_Intravascular_Coagulation
creation_date: '2026-02-12T19:38:17Z'
updated_date: '2026-02-12T19:38:17Z'
curation_status: CANDIDATE
notes: >-
  Rare but well-documented complication of advanced/metastatic melanoma. DIC
  typically occurs with widely disseminated disease or bone marrow infiltration.
  Multiple mechanistic pathways link melanoma biology to coagulation activation,
  including tissue factor overexpression (amplified by BRAF V600E), cancer
  procoagulant, and procoagulant microvesicle shedding. Only a handful of
  melanoma-DIC cases are reported in the literature as of 2021, but subclinical
  coagulation activation is common in advanced melanoma.

disease_a:
  slug: Malignant_Melanoma
  preferred_term: melanoma
  term:
    id: MONDO:0005105
    label: melanoma

disease_b:
  slug: Disseminated_Intravascular_Coagulation
  preferred_term: disseminated intravascular coagulation
  term:
    id: MONDO:0001243
    label: disseminated intravascular coagulation

directionality: A_BEFORE_B

hypotheses:
- description: >-
    Hypothesis: melanoma cells constitutively express tissue factor (TF) and
    expose phosphatidylserine (PS), driving extrinsic coagulation cascade
    activation that can progress to DIC in advanced disease. BRAF V600E
    mutation further upregulates TF expression and thrombin generation.
  evidence:
  - reference: PMID:31095038
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Disseminated intravascular coagulation is a complex and potentially
      lethal complication of malignancy, in which the fundamental abnormality
      is excessive activation of the coagulation system.
    explanation: >-
      Systematic review confirms DIC in melanoma results from excessive
      coagulation system activation.
  - reference: PMID:31041800
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Cancer often leads to the activation of coagulation, manifesting as
      disseminated intravascular coagulation (DIC) in its most extreme form.
    explanation: >-
      Review establishes cancer-associated coagulation activation as the
      underlying mechanism of DIC.
  pathophysiology:
  - name: Tissue factor overexpression by melanoma cells
    description: >-
      Melanoma cells constitutively express tissue factor (TF) on their
      surface, in contrast to normal melanocytes. TF initiates the extrinsic
      coagulation cascade, generating thrombin and promoting systemic
      coagulation activation. BRAF V600E mutation amplifies TF expression.
    biological_processes:
    - preferred_term: blood coagulation, extrinsic pathway
      term:
        id: GO:0007598
        label: blood coagulation, extrinsic pathway
    - preferred_term: positive regulation of blood coagulation
      term:
        id: GO:0030194
        label: positive regulation of blood coagulation
    gene_products:
    - preferred_term: Tissue Factor
      term:
        id: NCIT:C17197
        label: Tissue Factor
    - preferred_term: B-Raf Protein
      term:
        id: NCIT:C17476
        label: Serine/Threonine-Protein Kinase B-Raf
    evidence:
    - reference: PMID:19550359
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        Flow cytometry analyses showed constitutive TF expression by both
        cell lines, in contrast to negative staining observed for the
        nontumorigenic melanocyte lineage, melan-A.
      explanation: >-
        Melanoma cell lines constitutively express TF while normal
        melanocytes do not, establishing tumor-specific procoagulant
        activity.
    - reference: PMID:19550359
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        simultaneous TF expression and PS exposure are responsible for the
        highly procoagulant pattern of the aggressive melanoma cell lines
        B16F10 and WM-266-4.
      explanation: >-
        Combined TF and phosphatidylserine exposure drives the
        procoagulant phenotype of melanoma cells.
    - reference: PMID:26504080
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        the B-Raf(V600E) mutation in metastatic melanoma cells
        up-regulated tissue factor (TF) expression on cell membranes and
        promoted thrombin production.
      explanation: >-
        BRAF V600E directly increases TF expression and thrombin
        generation in melanoma cells.
    - reference: PMID:31467489
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        Dabrafenib and Trametinib caused the down-regulation of TF in
        both cell lines A-375 and SK-MEL-28.
      explanation: >-
        BRAF/MEK inhibitors reduce TF expression, providing
        pharmacological confirmation that MAPK pathway drives TF in
        melanoma.
    - reference: PMID:31467489
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        The present study provides the first in vitro observation that
        tissue factor expressed in melanoma cells may contribute to the
        modulation of the coagulation state of patients in the treatment
        with BRAF inhibitors.
      explanation: >-
        Links melanoma TF expression to clinical coagulation state and
        treatment response.

  - name: Cancer procoagulant (CP) direct factor X activation
    description: >-
      Cancer procoagulant (CP), a cysteine proteinase, directly activates
      coagulation factor X independently of both the intrinsic and extrinsic
      coagulation pathways. CP is present in all melanoma samples but absent
      in benign melanocytic lesions, and is markedly elevated in metastases
      compared to primary tumors.
    biological_processes:
    - preferred_term: blood coagulation
      term:
        id: GO:0007596
        label: blood coagulation
    - preferred_term: proteolysis
      term:
        id: GO:0006508
        label: proteolysis
    evidence:
    - reference: PMID:3536081
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        CP activity was detectable in extracts and cell suspensions from
        all 32 patients studied and was higher in extracts from metastases
        (14.8 +/- 3.9 units/mg protein) than from the primary tumors (3.7
        +/- 1.0 units/mg protein).
      explanation: >-
        Cancer procoagulant is universally present in melanoma and
        4-fold higher in metastases, explaining increased DIC risk with
        advanced disease.
    - reference: PMID:3536081
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        no CP activity or antigen was detected in extracts from six
        benign melanocytic lesions.
      explanation: >-
        CP is specific to malignant melanoma, absent in benign lesions,
        confirming its association with the malignant phenotype.
    - reference: PMID:3536081
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        CP activity was independent of both the intrinsic and extrinsic
        pathways of blood coagulation, using factor IX and factor VII
        deficient plasmas, and was inhibited by the cysteine proteinase
        inhibitors iodoacetamide and HgCl2.
      explanation: >-
        CP activates factor X through a pathway independent of tissue
        factor and factor VII, representing an additional procoagulant
        mechanism beyond TF.
    - reference: PMID:9518049
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        CP is a cysteine proteinase that is found in malignant and fetal
        (human amnion-chorion) tissue; it has not been found in normally
        differentiated tissue.
      explanation: >-
        Review confirms CP is restricted to malignant and fetal tissue,
        absent in normal differentiated tissue.
    - reference: PMID:9518049
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        antibodies to CP block the metastatic seeding of lung colonies
        in vivo and diminish the viability of tumor cells in vitro.
      explanation: >-
        Anti-CP antibodies block metastasis in vivo, demonstrating the
        functional significance of CP in tumor biology.
    - reference: PMID:1690950
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        these results support the concept that a tumor cell-associated,
        thrombin-generating pathway exists in situ in malignant melanoma
        tissue that includes Factor X but neither tissue factor nor
        Factor VII.
      explanation: >-
        Immunohistochemical evidence of a Factor X-dependent but
        TF/FVII-independent thrombin-generating pathway in melanoma
        in situ, consistent with cancer procoagulant mechanism.

  - name: Procoagulant microvesicle shedding
    description: >-
      Malignant melanocytes shed microvesicles at approximately twice the
      rate of normal melanocytes. These tumor-derived microvesicles carry
      tissue factor and accelerate thrombus formation in a TF-dependent
      manner, contributing to systemic coagulation activation.
    biological_processes:
    - preferred_term: extracellular vesicle biogenesis
      term:
        id: GO:0140112
        label: extracellular vesicle biogenesis
    - preferred_term: blood coagulation
      term:
        id: GO:0007596
        label: blood coagulation
    evidence:
    - reference: PMID:21800005
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        Tumour cells exhibit a two-fold higher rate of MVs production as
        compared to melan-a.
      explanation: >-
        Malignant melanocytes produce twice as many microvesicles as
        normal melanocytes.
    - reference: PMID:21800005
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        melanoma- but not melanocyte-derived MVs strongly accelerate
        thrombus formation in a TF-dependent manner, and accumulate at the
        site of vascular injury.
      explanation: >-
        Melanoma-derived microvesicles are prothrombotic in vivo in an
        arterial thrombosis model, mechanistically linking tumor MV
        shedding to coagulation activation.
    - reference: PMID:21800005
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        malignant transformation in melanocytes increases the production
        of procoagulant MVs, which may contribute for a variety of
        coagulation-related protumoural responses.
      explanation: >-
        Establishes that malignant transformation itself drives
        procoagulant MV production.
    - reference: PMID:18292996
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        significantly increased levels of TF-specific procoagulant
        activity (PCA) of plasma MPs in five patients presenting with
        overt disseminated intravascular coagulation (DIC) due to an
        underlying malignancy, including non-small-cell lung cancer (n =
        1), melanoma (n = 1), prostate cancer (n = 2), and acute
        promyelocytic leukemia (n = 1).
      explanation: >-
        Directly demonstrates elevated TF-positive microparticles in a
        melanoma patient with overt DIC.
    - reference: PMID:18292996
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        response of their malignancies to specific anti-cancer therapy
        was paralleled by resolution of overt DIC and a significant
        decline in MP-associated TF PCA.
      explanation: >-
        Resolution of DIC tracked with decline in TF-positive
        microparticles, supporting a causal role for tumor-derived
        procoagulant microparticles.

- description: >-
    Hypothesis: cytokine-mediated systemic inflammation in advanced melanoma
    activates endothelial tissue factor expression and suppresses natural
    anticoagulant pathways, contributing to consumptive coagulopathy. DIC
    in cancer is characterized by systemic intravascular coagulation activation
    with simultaneous consumption of clotting factors and platelets.
  evidence:
  - reference: PMID:31041800
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      DIC is characterized by systemic intravascular coagulation activation
      (leading to deposition of intravascular platelets and fibrin) and
      simultaneous consumption of coagulation proteins and thrombocytes
      (which may cause bleeding complications).
    explanation: >-
      Defines the consumptive mechanism underlying DIC in cancer patients.
  - reference: PMID:11583315
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      advanced malignancies (p = .027), breast cancer (p = .038) and the
      presence of necrosis in the tumor specimen (p = .004), emerged as
      independent factors significantly related to the occurrence of DIC in
      patients with solid tumors.
    explanation: >-
      Advanced disease stage and tumor necrosis are independent risk
      factors for DIC, supporting inflammation-driven coagulopathy.
  pathophysiology:
  - name: Consumptive coagulopathy in advanced malignancy
    description: >-
      Advanced melanoma with high tumor burden drives systemic coagulation
      activation through inflammatory cytokines and tumor necrosis. This
      leads to consumption of clotting factors and platelets, producing the
      characteristic DIC pattern of concurrent bleeding and thrombosis.
    biological_processes:
    - preferred_term: inflammatory response
      term:
        id: GO:0006954
        label: inflammatory response
    - preferred_term: blood coagulation
      term:
        id: GO:0007596
        label: blood coagulation
    - preferred_term: platelet activation
      term:
        id: GO:0030168
        label: platelet activation
    evidence:
    - reference: PMID:11583315
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Thrombocytopenia, hypofibrinogemia, elevated D-dimer and
        fibrinogen degradation products were the most common coagulation
        abnormalities encountered in patients with DIC.
      explanation: >-
        Identifies the laboratory hallmarks of consumptive coagulopathy
        in cancer-associated DIC.

association_signals:
- source: LITERATURE
  method: LITERATURE_ASSOCIATION
  population: >-
    1,117 consecutive patients with solid tumors evaluated for DIC
    (University of Tennessee, 2001).
  directionality: A_BEFORE_B
  statistics:
    metrics:
    - metric_type: PREVALENCE
      metric_value: 0.068
      notes: >-
        76 of 1,117 solid tumor patients (6.8%) diagnosed with DIC.
        Includes all solid tumor types, not melanoma-specific.
    evidence:
    - reference: PMID:11583315
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Of these patients, 76 (6.8%) were diagnosed with DIC.
      explanation: >-
        Establishes DIC prevalence in solid tumors at approximately 7%.
- source: LITERATURE
  method: LITERATURE_ASSOCIATION
  population: >-
    Systematic review of all published melanoma-associated DIC cases
    (Haggstrom et al., Melanoma Res, 2019).
  directionality: A_BEFORE_B
  notes: >-
    DIC is rare in melanoma; only a handful of cases documented in literature
    as of 2019. The review highlights that DIC typically portends poor
    prognosis in melanoma.
  statistics:
    evidence:
    - reference: PMID:31095038
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        It is a rare complication of melanoma which can be difficult to
        diagnose in some circumstances, leading to delay in treatment.
      explanation: >-
        Systematic review establishes DIC as a rare but recognized
        complication of melanoma.
    - reference: PMID:31095038
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Disseminated intravascular coagulation is a rare complication of
        melanoma that typically portends poor prognosis.
      explanation: DIC in melanoma carries poor prognosis.
- source: LITERATURE
  method: LITERATURE_ASSOCIATION
  population: >-
    Case report: 33-year-old woman with BRAF V600E-mutated metastatic
    melanoma presenting with fulminant DIC (Chuang et al., 2019).
  directionality: A_BEFORE_B
  notes: >-
    DIC was the initial presentation leading to melanoma diagnosis. Patient
    had concurrent hemorrhagic and thrombotic manifestations. DIC resolved
    with dabrafenib + trametinib treatment.
  statistics:
    evidence:
    - reference: PMID:31093395
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        a 33-year-old woman with BRAF V600E-mutated metastatic melanoma who
        presented in fulminant DIC with concurrent hemorrhagic and
        thrombotic manifestations
      explanation: >-
        Case report of fulminant DIC as initial presentation of
        BRAF-mutated metastatic melanoma.
- source: LITERATURE
  method: LITERATURE_ASSOCIATION
  population: >-
    Case report: 30-year-old female with bone marrow metastatic melanoma
    presenting with DIC (Gbadamosi et al., 2018).
  directionality: A_BEFORE_B
  notes: >-
    BM biopsy showed extensive melanoma involvement in the absence of
    visceral or brain metastasis. Responded to nivolumab + ipilimumab.
  statistics:
    evidence:
    - reference: PMID:29796327
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        She was found to be bicytopenic and in disseminated intravascular
        coagulopathy (DIC). Surprisingly, BM biopsy showed extensive
        involvement by metastatic malignant melanoma in the absence of
        visceral or brain metastasis.
      explanation: >-
        Bone marrow infiltration by melanoma can cause DIC even without
        widespread visceral disease.
- source: LITERATURE
  method: LITERATURE_ASSOCIATION
  population: >-
    Case report: 79-year-old woman with metastatic mucosal melanoma and DIC
    (Luna Pais et al., 2021).
  directionality: A_BEFORE_B
  notes: >-
    Third documented case of melanoma with DIC at presentation. Only case
    achieving complete remission with immunotherapy.
  statistics:
    evidence:
    - reference: PMID:34659846
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        This is the third case of melanoma with disseminated intravascular
        coagulation at presentation and the second case treated with
        immunotherapy in the literature, but the only one achieving disease
        remission.
      explanation: >-
        Confirms rarity of melanoma-DIC and documents successful
        immunotherapy treatment.
- source: LITERATURE
  method: LITERATURE_ASSOCIATION
  population: >-
    Case report: 34-year-old male with fulminant metastatic melanoma,
    microangiopathic hemolytic anemia, and DIC (Bhagwati et al., 1998).
  directionality: A_BEFORE_B
  notes: >-
    First recognized case of metastatic melanoma with microangiopathic
    hemolytic anemia. Patient expired 3 weeks after diagnosis despite
    aggressive treatment.
  statistics:
    evidence:
    - reference: PMID:9608358
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        A 34-year-old male acutely presented with widely disseminated
        malignant melanoma, a microangiopathic hemolytic anemia, and
        disseminated intravascular coagulation.
      explanation: >-
        First documented case of melanoma with concurrent MAHA and DIC.
    - reference: PMID:9608358
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        This is the first recognized case of metastatic melanoma occurring
        in association with a microangiopathic hemolytic anemia.
      explanation: >-
        Establishes MAHA as a rare but recognized manifestation of
        melanoma-associated DIC.
- source: LITERATURE
  method: LITERATURE_ASSOCIATION
  population: >-
    95 consecutive stage IV melanoma patients followed in a dermatology
    department (Limoges, France, 2005-2007).
  directionality: A_BEFORE_B
  notes: >-
    VTE prevalence in stage IV melanoma comparable to lung and GI cancers,
    reflecting subclinical coagulation activation even without overt DIC.
  statistics:
    metrics:
    - metric_type: PREVALENCE
      metric_value: 0.252
      metric_ci_lower: 0.165
      metric_ci_upper: 0.34
      notes: >-
        24 VTE events in 95 stage IV melanoma patients (25.2%).
    evidence:
    - reference: PMID:20629849
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Twenty-four VTE events were found [25.2% (CI: 16.5-34)].
      explanation: >-
        High VTE prevalence in stage IV melanoma demonstrates
        widespread coagulation activation in advanced disease.
    - reference: PMID:20629849
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        We found as high a prevalence of VTE in stage IV melanoma as in
        lung and gastrointestinal cancers.
      explanation: >-
        Melanoma VTE risk is comparable to other high-risk solid tumors.
- source: LITERATURE
  method: LITERATURE_ASSOCIATION
  population: >-
    533 melanoma patients analyzed for D-dimer levels and clinical
    outcomes (University Medical Center Mannheim, Germany).
  directionality: A_BEFORE_B
  notes: >-
    Elevated D-dimer indicates activated coagulation and fibrinolysis,
    representing subclinical coagulation activation that can precede overt DIC.
  statistics:
    metrics:
    - metric_type: PREVALENCE
      metric_value: 0.272
      notes: >-
        145 of 533 melanoma patients (27.2%) had elevated D-dimer (>0.6 mg/L).
    - metric_type: HR
      metric_value: 2.89
      metric_ci_lower: 2.07
      metric_ci_upper: 7.56
      notes: >-
        Univariate HR for progression-free survival with elevated D-dimer.
    evidence:
    - reference: PMID:27813063
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        145 of the total 533 patients (27.2%) were identified with
        elevated plasma D-dimer levels.
      explanation: >-
        Over a quarter of melanoma patients show elevated D-dimer,
        indicating widespread subclinical coagulation activation.
    - reference: PMID:27813063
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        elevated D-dimer levels were significantly associated with
        decreased PFS (HR:2.89, 95% CI (2.07-7.56), p < 0.0001) and OS
        (HR:2.22, 95% CI (1.06-4.57), p = 0.035).
      explanation: >-
        D-dimer elevation predicts worse progression-free and overall
        survival in melanoma.
- source: LITERATURE
  method: LITERATURE_ASSOCIATION
  population: >-
    61 melanoma patients (stage I-IV) and 50 healthy controls assessed
    for coagulation assays (Istanbul University, Turkey).
  directionality: A_BEFORE_B
  notes: >-
    Elevated fibrinogen as a prognostic biomarker reflecting coagulation
    activation in melanoma. 54% of patients were metastatic (stage IV).
  statistics:
    metrics:
    - metric_type: OTHER
      metric_value: 0.58
      notes: >-
        1-year survival rate for patients with high fibrinogen levels
        (58%), compared to 88% for those with normal levels (P=0.031).
    evidence:
    - reference: PMID:22889867
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        only elevated plasma F levels had a significantly adverse effect
        on survival among the coagulation parameters (P=0.031). The
        1-year survival rates for patients with high and normal F levels
        were 58 and 88%, respectively.
      explanation: >-
        Elevated fibrinogen independently predicts decreased survival
        in melanoma, linking coagulation activation to prognosis.
    - reference: PMID:22889867
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        changes in the coagulation-fibrinolytic system are often present
        in melanoma and elevation in the plasma F level is associated
        with decreased survival.
      explanation: >-
        Confirms that coagulation-fibrinolytic changes are common in
        melanoma patients.

phenotypes:
- name: Thrombocytopenia
  description: >-
    Consumption of platelets due to systemic intravascular coagulation
    activation, a hallmark of DIC in melanoma patients.
  phenotype_term:
    preferred_term: Thrombocytopenia
    term:
      id: HP:0001873
      label: Thrombocytopenia
  evidence:
  - reference: PMID:11583315
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Thrombocytopenia, hypofibrinogemia, elevated D-dimer and fibrinogen
      degradation products were the most common coagulation abnormalities
      encountered in patients with DIC.
    explanation: >-
      Thrombocytopenia is among the most common coagulation abnormalities
      in cancer-associated DIC.
  - reference: PMID:31041800
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      simultaneous consumption of coagulation proteins and thrombocytes
      (which may cause bleeding complications).
    explanation: >-
      Platelet consumption is a defining feature of DIC pathophysiology.

- name: Hypofibrinogenemia
  description: >-
    Depletion of fibrinogen due to consumptive coagulopathy in DIC,
    documented in melanoma-DIC case reports with fibrinogen levels as low
    as less than 30 mg/dL.
  phenotype_term:
    preferred_term: Hypofibrinogenemia
    term:
      id: HP:0011900
      label: Hypofibrinogenemia
  evidence:
  - reference: PMID:11583315
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Thrombocytopenia, hypofibrinogemia, elevated D-dimer and fibrinogen
      degradation products were the most common coagulation abnormalities
      encountered in patients with DIC.
    explanation: >-
      Hypofibrinogenemia is a hallmark lab finding in cancer-associated DIC.

- name: Abnormal bleeding
  description: >-
    Hemorrhagic manifestations including hematochezia, hematemesis, epistaxis,
    and easy bruising, resulting from consumption of clotting factors.
  phenotype_term:
    preferred_term: Abnormal bleeding
    term:
      id: HP:0001892
      label: Abnormal bleeding
  evidence:
  - reference: PMID:31093395
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      a 33-year-old woman with BRAF V600E-mutated metastatic melanoma who
      presented in fulminant DIC with concurrent hemorrhagic and thrombotic
      manifestations
    explanation: >-
      Hemorrhagic manifestations are a presenting feature of
      melanoma-associated DIC.
  - reference: PMID:29796327
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      30-year-old female who presented to the hospital with back pain,
      low-grade fever, and easy bruising.
    explanation: Easy bruising as presenting symptom of melanoma-DIC.
  - reference: PMID:31041800
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      the ongoing consumption may result in low levels of platelets and
      coagulation factors, and bleeding complications (frequently localized
      at the site of the tumor or distant metastases) may be the first
      clinical manifestation of DIC.
    explanation: >-
      Bleeding complications may be the initial presentation of
      cancer-associated DIC.

- name: Thrombosis
  description: >-
    Microvascular and macrovascular thrombotic complications including
    digital ischemia, bowel necrosis from microthrombi, and venous
    thromboembolism.
  phenotype_term:
    preferred_term: Thrombosis
    term:
      id: HP:0001907
      label: Thromboembolism
  evidence:
  - reference: PMID:31041800
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      An alternative clinical scenario is dominated by thrombotic
      complications, ranging from clinically manifest vascular thrombosis to
      microvascular platelet plugs.
    explanation: >-
      Thrombotic manifestations are a recognized presentation of
      cancer-associated DIC.
  - reference: PMID:31093395
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      a 33-year-old woman with BRAF V600E-mutated metastatic melanoma who
      presented in fulminant DIC with concurrent hemorrhagic and thrombotic
      manifestations
    explanation: >-
      Concurrent thrombotic manifestations in melanoma-DIC case.
  - reference: PMID:20629849
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Twenty-four VTE events were found [25.2% (CI: 16.5-34)].
    explanation: >-
      High VTE prevalence in stage IV melanoma demonstrates
      thromboembolism as a common complication.

- name: Microangiopathic hemolytic anemia
  description: >-
    Red blood cell fragmentation due to microvascular fibrin deposition
    and mechanical shearing, documented in melanoma-associated DIC.
  phenotype_term:
    preferred_term: Microangiopathic hemolytic anemia
    term:
      id: HP:0001937
      label: Microangiopathic hemolytic anemia
  evidence:
  - reference: PMID:9608358
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A 34-year-old male acutely presented with widely disseminated
      malignant melanoma, a microangiopathic hemolytic anemia, and
      disseminated intravascular coagulation.
    explanation: >-
      First documented case of melanoma with concurrent MAHA and DIC.
  - reference: PMID:9608358
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This is the first recognized case of metastatic melanoma occurring
      in association with a microangiopathic hemolytic anemia.
    explanation: >-
      Establishes MAHA as a rare but recognized complication of
      melanoma-associated DIC.

- name: Pancytopenia
  description: >-
    Reduction in all blood cell lineages, observed in melanoma-DIC cases
    with bone marrow infiltration.
  phenotype_term:
    preferred_term: Pancytopenia
    term:
      id: HP:0001876
      label: Pancytopenia
  evidence:
  - reference: PMID:29796327
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      She was found to be bicytopenic and in disseminated intravascular
      coagulopathy (DIC).
    explanation: >-
      Cytopenias documented in bone marrow metastatic melanoma with DIC.