Hemoglobin (Hb) and Cancer-Associated Anemia

A persistent drop in hemoglobin levels — especially in the absence of obvious causes like menstruation or bleeding ulcers — should raise concern. In oncology, anemia often emerges in one of three contexts:

1. Chronic blood loss (e.g., colorectal cancer)
2. Bone marrow infiltration (e.g., leukemia, lymphoma, metastasis)
3. Chronic disease anemia (linked to inflammatory cytokines suppressing erythropoiesis)

Low hemoglobin can be the first lab abnormality in gastrointestinal or renal tumors, especially in older patients with vague fatigue.

Parameter	Normal Range (M/F)	Concerning Trend	Potential Cancer Implication
Hemoglobin	130–170 / 120–150 g/L	↓ < 100 g/L	Colon, kidney, bone marrow involvement

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White Blood Cell Count (WBC) in Hematologic and Solid Tumors

Abnormalities in white blood cell count can appear as either leukocytosis or leukopenia. In acute leukemias, WBC may be dramatically elevated, often exceeding 50,000/μL. In contrast, advanced cancers or marrow failure (e.g., after metastasis) may cause profound leukopenia.

In chronic solid tumors, mild leukocytosis may reflect tumor-related inflammation or paraneoplastic leukemoid reactions.

Parameter	Normal Range	Abnormal Trend	Possible Causes
WBC	4.0–10.0 ×10⁹/L	↑ > 20 ×10⁹/L	Leukemia, paraneoplastic syndrome
		↓ < 3 ×10⁹/L	Marrow suppression, lymphoma

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Neutrophil-to-Lymphocyte Ratio (NLR) as Prognostic Marker

Rather than looking at absolute counts, the NLR has emerged as a dynamic marker of systemic inflammation and poor prognosis. In many cancers (colorectal, lung, gastric), a high NLR (e.g., >3.5) correlates with tumor progression and poor survival. It reflects neutrophil-driven inflammation and lymphocyte-mediated immune suppression.

This ratio is especially helpful in pre-operative assessments and treatment planning.

Parameter	Normal NLR	Elevated NLR	Clinical Interpretation
Neutrophil / Lymphocyte	~1.5–2.5	>3.5	Inflammation, immune dysfunction, cancer

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Platelets (PLT) and Paraneoplastic Thrombocytosis

Platelets can both reflect and fuel cancer processes. Elevated platelet counts (thrombocytosis) are associated with tumors such as lung, ovarian, and GI cancers, often due to tumor secretion of IL-6. Inversely, low platelet counts may signal bone marrow infiltration or hematologic malignancy.

Thrombocytosis is a poor prognostic marker in many cancers and may predict metastasis.

Parameter	Normal Range	Abnormal Level	Implication
Platelets	150–400 ×10⁹/L	↑ > 450 ×10⁹/L	Lung, ovarian, colon cancer
		↓ < 100 ×10⁹/L	Leukemia, marrow failure

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Erythrocyte Sedimentation Rate (ESR) and Cancer Inflammation

ESR is a crude but sensitive marker for chronic inflammation. Many cancers — particularly lymphomas, multiple myeloma, and solid tumors with large necrotic cores — are associated with persistently elevated ESR. Its rise is due to altered plasma proteins (especially fibrinogen), often in response to cytokines like IL-1 and TNF-alpha.

Though non-specific, ESR over 50 mm/hr, especially in the absence of infection, often prompts imaging in oncology.

Parameter	Normal Range (M/F)	High Risk Level	Common Cancer Context
ESR	<15 / <20 mm/hr	>50 mm/hr	Myeloma, lymphoma, solid tumors

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C-Reactive Protein (CRP): The Acute-Phase Driver in Tumors

CRP rises sharply in systemic inflammation. In cancer, elevated CRP correlates with tumor burden, necrosis, and cytokine release. It is especially high in pancreatic cancer, renal carcinoma, and advanced-stage tumors. Elevated CRP at diagnosis or during therapy often correlates with worse prognosis and shorter progression-free survival.

Parameter	Normal Range	Oncology Concern	Role in Management
CRP	<5 mg/L	>10–20 mg/L	Prognosis, treatment response

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LDH (Lactate Dehydrogenase): A Marker of Tumor Burden

LDH reflects tissue turnover and hypoxic metabolism. It is commonly elevated in lymphomas, melanomas, testicular cancer, and any cancer with aggressive growth or liver metastasis. LDH is part of the standard Ann Arbor staging for lymphomas and used in monitoring response to treatment.

Very high LDH often correlates with tumor lysis, necrosis, or hepatic involvement.

Parameter	Normal Range	Significant Elevation	Cancer Association
LDH	<250 U/L	>500 U/L	Lymphoma, melanoma, metastases

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Ferritin: More Than Iron Storage

While ferritin is best known as an iron storage protein, in cancer it functions as an acute-phase reactant. Elevated ferritin can occur in leukemia, lymphoma, hepatocellular carcinoma, and advanced inflammation. In hemophagocytic syndromes (HLH), which can be cancer-associated, ferritin can skyrocket to thousands.

Chronically high ferritin without iron overload or liver disease should prompt oncologic evaluation.

Parameter	Normal Range	Concerning Level	Associated Conditions
Ferritin	20–300 ng/mL	>500–1000 ng/mL	Hematologic malignancy, HLH, liver cancer

Alkaline Phosphatase (ALP): A Marker of Bone and Liver Infiltration

Alkaline phosphatase (ALP) is a key enzyme involved in bone turnover and bile duct function. While mild ALP elevation can occur in benign conditions like healing fractures or fatty liver, a persistently high ALP level — especially above twice the upper limit of normal (ULN) — may signal bone metastases or infiltration of the liver by a tumor.

In cancers like prostate, breast, lung, and multiple myeloma, ALP can be a frontline signal of skeletal involvement, often before radiologic signs appear.

In hepatobiliary tumors (e.g., cholangiocarcinoma), elevation may precede bilirubin changes, especially if bile ducts are compressed externally.

Parameter	Normal Range (Adult)	Red Flag Values	Possible Malignancies
ALP	30–120 U/L	>250–300 U/L	Bone mets (breast, prostate), liver tumors

Clinical tip: If ALP is elevated alongside normal AST/ALT, consider isolated bone involvement. If ALP + GGT + Bilirubin are elevated — likely liver/biliary pathology.

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AST, ALT: Transaminases in Liver-Involved Cancer

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are intracellular enzymes released when hepatocytes are damaged. While commonly used to evaluate hepatitis and alcohol-induced liver injury, moderate elevations in AST/ALT without classic hepatitis markers may indicate:

• Liver metastases (commonly from colon, breast, or lung primaries)
• Primary liver cancers, including hepatocellular carcinoma (HCC)
• Drug-induced liver injury from chemotherapy

ALT is more liver-specific; AST is also present in muscle and cardiac tissue, so isolated AST elevation may be misleading.

Parameter	Normal Range	Suspicious Levels	Relevance in Cancer
ALT	<35–45 U/L	>100 U/L	HCC, liver mets, chemo liver toxicity
AST	<35–45 U/L	>100 U/L	Less specific; interpret with ALT

Note: In liver-dominant metastasis, transaminase elevation often coincides with fatigue, weight loss, and hepatomegaly.

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Bilirubin: A Signal of Biliary Obstruction or Liver Failure

Bilirubin, a byproduct of hemoglobin breakdown, rises when bile flow is obstructed, or liver function is impaired. In oncology, elevated bilirubin may suggest:

• Obstruction by tumors (e.g., pancreatic head carcinoma compressing bile duct)
• Massive liver infiltration (e.g., in metastatic breast or colon cancer)
• Hemolysis due to cancer-related anemia or microangiopathy

Elevation of direct (conjugated) bilirubin is more common in malignancy, due to cholestasis or hepatocellular dysfunction.

Parameter	Normal Range	Red Flags	Typical Contexts
Total Bilirubin	<1.2 mg/dL	>2.0–3.0 mg/dL	Pancreatic cancer, HCC, liver mets
Direct Bilirubin	<0.4 mg/dL	>1.0 mg/dL	Obstruction (cholangiocarcinoma)

Clinical indicator: Jaundice + weight loss + elevated bilirubin = urgent imaging to rule out biliary obstruction from cancer.

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Gamma-Glutamyl Transferase (GGT): Cholestasis and Tumor Pressure

GGT is an enzyme more specific to the biliary tree than ALP. While both rise in cholestasis, GGT helps differentiate liver/biliary causes from bone disease when ALP is elevated.

A high GGT with high ALP — and normal calcium/phosphate — suggests biliary obstruction or liver metastases.

Parameter	Normal Range	High-Risk Level	Oncologic Significance
GGT	<50 U/L (men)	>150–200 U/L	Liver mets, pancreatic head tumor

Also rises with chronic alcohol use, so context is crucial.

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Tumor Markers: Context-Dependent Tools, Not Screening Tests

Tumor markers are biochemical substances secreted either by tumor cells or by the body in response to malignancy. These are not reliable for early detection, but when combined with imaging and clinical context, they provide immense diagnostic and monitoring value.

Here’s a breakdown of common markers and their use:

Marker	Primary Use	Main Cancers	Notes
PSA	Prostate screening and monitoring	Prostate cancer	Elevated in BPH too
CA-125	Monitoring ovarian masses	Ovarian cancer	Not specific alone
CEA	Monitoring recurrence	Colorectal, lung, breast	↑ in smokers
CA 19-9	Pancreatic mass assessment	Pancreatic, gastric, biliary	↑ in cholestasis too
AFP	Diagnosis of liver/testicular cancer	HCC, germ cell tumors	Track treatment response
β-hCG	Testicular, choriocarcinoma marker	Germ cell tumors, pregnancy cancers	Can be part of triple-marker panel
NSE	Neuroendocrine marker	Small-cell lung cancer	Less used alone

These should never be interpreted without imaging or histology. For example, a CEA of 15 ng/mL may mean recurrence after colon cancer resection — but not in isolation.

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D-dimer: Hypercoagulability as a Paraneoplastic Signal

D-dimer is a fibrin degradation product, typically used in evaluating thrombosis. However, in cancer, elevated D-dimer may be the first biochemical sign of:

• Hidden malignancy in patients with idiopathic venous thromboembolism
• Advanced-stage tumors with systemic activation of coagulation (Trousseau’s syndrome)
• High tumor burden or necrosis

Parameter	Normal Range	Elevated Value	Associated Cancer Findings
D-dimer	<0.5 μg/mL FEU	>1.0–2.0 μg/mL	Pancreatic, gastric, lung, metastasis

D-dimer >3.0 in a patient without thrombosis or infection should raise strong suspicion for occult malignancy.

When Blood Tells the Truth Before Imaging

Abnormalities in these blood markers are not diagnostic alone, but in combination — especially with persistent symptoms — they guide early cancer detection, staging, and even therapeutic decisions. As a clinical oncologist, I rely on these markers not just to suspect disease, but also to track the silent relapses and subtle progressions invisible on scans.

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